Blood Banking

Photo by Daniel Gay

The US Food and Drug Administration (FDA) has approved 2 Grifols blood screening assays—Procleix Ultrio Elite and Procleix WNV.

Procleix WNV is a qualitative in vitro nucleic acid assay for the detection of West Nile virus RNA in plasma and serum of human blood donors.

Procleix Ultrio Elite is a blood screening assay that delivers simultaneous results for human immunodeficiency virus type 1, hepatitis C virus, and hepatitis B virus. It also detects human immunodeficiency virus type 2.

Procleix Ultrio Elite can be used to test pools of plasma composed of up to 96 individual donations from donors of source plasma.

Grifols will begin commercializing the Procleix Ultrio Elite and Procleix WNV assays in the US later this year.

“These FDA approvals demonstrate our ongoing commitment to expand Grifols comprehensive nucleic acid testing (NAT) solutions portfolio to help labs administer NAT,” said Carsten Schroeder, president of Grifols’s Diagnostic Division.

Procleix Ultrio Elite and Procleix WNV will run on the fully automated NAT blood screening platform Procleix Panther system. The device is an integrated NAT system that fully automates all necessary steps to perform Procleix assays, from sample processing through amplification, detection, and data reduction.

“The addition of the Procleix Panther system with these assays will allow blood centers to efficiently screen for infectious diseases on one simple, automated platform while adapting to changes in donation volume and regulatory requirements,” Schroeder said.

Photo by Daniel Gay

The US Food and Drug Administration (FDA) has approved 2 Grifols blood screening assays—Procleix Ultrio Elite and Procleix WNV.

Procleix WNV is a qualitative in vitro nucleic acid assay for the detection of West Nile virus RNA in plasma and serum of human blood donors.

Procleix Ultrio Elite is a blood screening assay that delivers simultaneous results for human immunodeficiency virus type 1, hepatitis C virus, and hepatitis B virus. It also detects human immunodeficiency virus type 2.

Procleix Ultrio Elite can be used to test pools of plasma composed of up to 96 individual donations from donors of source plasma.

Grifols will begin commercializing the Procleix Ultrio Elite and Procleix WNV assays in the US later this year.

“These FDA approvals demonstrate our ongoing commitment to expand Grifols comprehensive nucleic acid testing (NAT) solutions portfolio to help labs administer NAT,” said Carsten Schroeder, president of Grifols’s Diagnostic Division.

Procleix Ultrio Elite and Procleix WNV will run on the fully automated NAT blood screening platform Procleix Panther system. The device is an integrated NAT system that fully automates all necessary steps to perform Procleix assays, from sample processing through amplification, detection, and data reduction.

“The addition of the Procleix Panther system with these assays will allow blood centers to efficiently screen for infectious diseases on one simple, automated platform while adapting to changes in donation volume and regulatory requirements,” Schroeder said.

Photo by Daniel Gay

The US Food and Drug Administration (FDA) has approved 2 Grifols blood screening assays—Procleix Ultrio Elite and Procleix WNV.

Procleix WNV is a qualitative in vitro nucleic acid assay for the detection of West Nile virus RNA in plasma and serum of human blood donors.

Procleix Ultrio Elite is a blood screening assay that delivers simultaneous results for human immunodeficiency virus type 1, hepatitis C virus, and hepatitis B virus. It also detects human immunodeficiency virus type 2.

Procleix Ultrio Elite can be used to test pools of plasma composed of up to 96 individual donations from donors of source plasma.

Grifols will begin commercializing the Procleix Ultrio Elite and Procleix WNV assays in the US later this year.

“These FDA approvals demonstrate our ongoing commitment to expand Grifols comprehensive nucleic acid testing (NAT) solutions portfolio to help labs administer NAT,” said Carsten Schroeder, president of Grifols’s Diagnostic Division.

Procleix Ultrio Elite and Procleix WNV will run on the fully automated NAT blood screening platform Procleix Panther system. The device is an integrated NAT system that fully automates all necessary steps to perform Procleix assays, from sample processing through amplification, detection, and data reduction.

“The addition of the Procleix Panther system with these assays will allow blood centers to efficiently screen for infectious diseases on one simple, automated platform while adapting to changes in donation volume and regulatory requirements,” Schroeder said.

Photo by Elise Amendola

Researchers have developed software that could enable more precise matching for blood transfusions, according to a paper published in The Lancet Haematology.

The software, bloodTyper, can automatically type red blood cell (RBC) and platelet antigens from whole-genome sequencing (WGS) data.

In repeated tests, bloodTyper produced results that were more than 99% concordant with results from conventional antigen typing methods.

The researchers said these results suggest bloodTyper could improve transfusion typing.

“[W]ith current technology, it is not cost-effective to do blood typing for all antigens,” said study author William Lane, MD, PhD, of Brigham and Women’s Hospital in Boston, Massachusetts.

“But the algorithm we have developed can be applied to type everyone for all relevant blood groups at a low cost once sequencing is obtained.”

Dr Lane and his colleagues first tested bloodTyper using data from the MedSeq Project—the first randomized trial of WGS in healthy adults.

Blood samples from 110 subjects underwent DNA isolation, WGS, and RBC and platelet antigen typing with bloodTyper. Samples also underwent single nucleotide polymorphism (SNP) array typing and serological typing.

The researchers compared results with these typing methods and found that bloodTyper was 99.5% concordant with serological and SNP typing across the first 20 MedSeq genomes.

Further refinement of bloodTyper enabled improved concordance for the remaining 90 genomes. The researchers said bloodTyper was 99.8% concordant with serological and SNP typing methods for 38 RBC and 22 platelet antigens (encoded by 17 RBC and 6 platelet genes).

The team made additional modifications to bloodTyper and tested it with 200 genomes from the INTERVAL study. This time, bloodTyper was 99.2% concordant with serological methods for typing of 21 RBC antigens encoded by 14 genes.

When the researchers adjusted for the lower depth of coverage for INTERVAL genomes compared to MedSeq genomes (15× and 30×, respectively), they observed 99.9% concordance between serological typing and bloodTyper.

“This approach has the potential to be one of the first routine clinical uses of genomics for medical care for patients needing blood transfusion,” said study author Connie M. Westhoff, PhD, of the New York Blood Center in New York, New York.

“It could prevent serious or even fatal complications because, once patients are sensitized, they have a life-long risk of hemolytic transfusion reactions if blood transfusion is needed in an emergency.”

Photo by Elise Amendola

Researchers have developed software that could enable more precise matching for blood transfusions, according to a paper published in The Lancet Haematology.

The software, bloodTyper, can automatically type red blood cell (RBC) and platelet antigens from whole-genome sequencing (WGS) data.

In repeated tests, bloodTyper produced results that were more than 99% concordant with results from conventional antigen typing methods.

The researchers said these results suggest bloodTyper could improve transfusion typing.

“[W]ith current technology, it is not cost-effective to do blood typing for all antigens,” said study author William Lane, MD, PhD, of Brigham and Women’s Hospital in Boston, Massachusetts.

“But the algorithm we have developed can be applied to type everyone for all relevant blood groups at a low cost once sequencing is obtained.”

Dr Lane and his colleagues first tested bloodTyper using data from the MedSeq Project—the first randomized trial of WGS in healthy adults.

Blood samples from 110 subjects underwent DNA isolation, WGS, and RBC and platelet antigen typing with bloodTyper. Samples also underwent single nucleotide polymorphism (SNP) array typing and serological typing.

The researchers compared results with these typing methods and found that bloodTyper was 99.5% concordant with serological and SNP typing across the first 20 MedSeq genomes.

Further refinement of bloodTyper enabled improved concordance for the remaining 90 genomes. The researchers said bloodTyper was 99.8% concordant with serological and SNP typing methods for 38 RBC and 22 platelet antigens (encoded by 17 RBC and 6 platelet genes).

The team made additional modifications to bloodTyper and tested it with 200 genomes from the INTERVAL study. This time, bloodTyper was 99.2% concordant with serological methods for typing of 21 RBC antigens encoded by 14 genes.

When the researchers adjusted for the lower depth of coverage for INTERVAL genomes compared to MedSeq genomes (15× and 30×, respectively), they observed 99.9% concordance between serological typing and bloodTyper.

“This approach has the potential to be one of the first routine clinical uses of genomics for medical care for patients needing blood transfusion,” said study author Connie M. Westhoff, PhD, of the New York Blood Center in New York, New York.

“It could prevent serious or even fatal complications because, once patients are sensitized, they have a life-long risk of hemolytic transfusion reactions if blood transfusion is needed in an emergency.”

Photo by Elise Amendola

Researchers have developed software that could enable more precise matching for blood transfusions, according to a paper published in The Lancet Haematology.

The software, bloodTyper, can automatically type red blood cell (RBC) and platelet antigens from whole-genome sequencing (WGS) data.

In repeated tests, bloodTyper produced results that were more than 99% concordant with results from conventional antigen typing methods.

The researchers said these results suggest bloodTyper could improve transfusion typing.

“[W]ith current technology, it is not cost-effective to do blood typing for all antigens,” said study author William Lane, MD, PhD, of Brigham and Women’s Hospital in Boston, Massachusetts.

“But the algorithm we have developed can be applied to type everyone for all relevant blood groups at a low cost once sequencing is obtained.”

Dr Lane and his colleagues first tested bloodTyper using data from the MedSeq Project—the first randomized trial of WGS in healthy adults.

Blood samples from 110 subjects underwent DNA isolation, WGS, and RBC and platelet antigen typing with bloodTyper. Samples also underwent single nucleotide polymorphism (SNP) array typing and serological typing.

The researchers compared results with these typing methods and found that bloodTyper was 99.5% concordant with serological and SNP typing across the first 20 MedSeq genomes.

Further refinement of bloodTyper enabled improved concordance for the remaining 90 genomes. The researchers said bloodTyper was 99.8% concordant with serological and SNP typing methods for 38 RBC and 22 platelet antigens (encoded by 17 RBC and 6 platelet genes).

The team made additional modifications to bloodTyper and tested it with 200 genomes from the INTERVAL study. This time, bloodTyper was 99.2% concordant with serological methods for typing of 21 RBC antigens encoded by 14 genes.

When the researchers adjusted for the lower depth of coverage for INTERVAL genomes compared to MedSeq genomes (15× and 30×, respectively), they observed 99.9% concordance between serological typing and bloodTyper.

“This approach has the potential to be one of the first routine clinical uses of genomics for medical care for patients needing blood transfusion,” said study author Connie M. Westhoff, PhD, of the New York Blood Center in New York, New York.

“It could prevent serious or even fatal complications because, once patients are sensitized, they have a life-long risk of hemolytic transfusion reactions if blood transfusion is needed in an emergency.”

Photo from UAB Hospital

The US Food and Drug Administration (FDA) has approved an additional use for the cobas Zika test.

The approval allows for the streamlined screening of multiple individual blood or plasma donations that have been pooled together.

The cobas Zika test is a qualitative in vitro nucleic acid screening test for the direct detection of Zika virus RNA in plasma specimens from blood donors.

The test is used with the cobas 6800/8800 systems, which are fully automated, high-volume systems that perform sample pooling, sample preparation (nucleic acid extraction and purification), and polymerase chain reaction amplification and detection.

Automated data management is performed by the cobas 6800/8800 software, which assigns a test result of non-reactive, reactive, or invalid.

Roche deployed the cobas Zika test in April 2016 under the FDA’s investigational new drug application protocol to screen blood donations collected in Puerto Rico.

This initial testing protocol enabled the reinstatement of blood services in Puerto Rico after concerns over high rates of Zika infection posed a threat to the blood supply.

The cobas Zika test received commercial approval from the FDA in October 2017, enabling routine use of the test to support individual donor screening efforts throughout Puerto Rico and the continental US.

“More than 6 million blood donations from the United States and Puerto Rico have been screened with the cobas Zika test since its initial release under the investigational new drug application protocol in 2016 and subsequent commercial approval in 2017,” said Uwe Oberlaender, head of Roche Molecular Diagnostics.

Photo from UAB Hospital

The US Food and Drug Administration (FDA) has approved an additional use for the cobas Zika test.

The approval allows for the streamlined screening of multiple individual blood or plasma donations that have been pooled together.

The cobas Zika test is a qualitative in vitro nucleic acid screening test for the direct detection of Zika virus RNA in plasma specimens from blood donors.

The test is used with the cobas 6800/8800 systems, which are fully automated, high-volume systems that perform sample pooling, sample preparation (nucleic acid extraction and purification), and polymerase chain reaction amplification and detection.

Automated data management is performed by the cobas 6800/8800 software, which assigns a test result of non-reactive, reactive, or invalid.

Roche deployed the cobas Zika test in April 2016 under the FDA’s investigational new drug application protocol to screen blood donations collected in Puerto Rico.

This initial testing protocol enabled the reinstatement of blood services in Puerto Rico after concerns over high rates of Zika infection posed a threat to the blood supply.

The cobas Zika test received commercial approval from the FDA in October 2017, enabling routine use of the test to support individual donor screening efforts throughout Puerto Rico and the continental US.

“More than 6 million blood donations from the United States and Puerto Rico have been screened with the cobas Zika test since its initial release under the investigational new drug application protocol in 2016 and subsequent commercial approval in 2017,” said Uwe Oberlaender, head of Roche Molecular Diagnostics.

Photo from UAB Hospital

The US Food and Drug Administration (FDA) has approved an additional use for the cobas Zika test.

The approval allows for the streamlined screening of multiple individual blood or plasma donations that have been pooled together.

The cobas Zika test is a qualitative in vitro nucleic acid screening test for the direct detection of Zika virus RNA in plasma specimens from blood donors.

The test is used with the cobas 6800/8800 systems, which are fully automated, high-volume systems that perform sample pooling, sample preparation (nucleic acid extraction and purification), and polymerase chain reaction amplification and detection.

Automated data management is performed by the cobas 6800/8800 software, which assigns a test result of non-reactive, reactive, or invalid.

Roche deployed the cobas Zika test in April 2016 under the FDA’s investigational new drug application protocol to screen blood donations collected in Puerto Rico.

This initial testing protocol enabled the reinstatement of blood services in Puerto Rico after concerns over high rates of Zika infection posed a threat to the blood supply.

The cobas Zika test received commercial approval from the FDA in October 2017, enabling routine use of the test to support individual donor screening efforts throughout Puerto Rico and the continental US.

“More than 6 million blood donations from the United States and Puerto Rico have been screened with the cobas Zika test since its initial release under the investigational new drug application protocol in 2016 and subsequent commercial approval in 2017,” said Uwe Oberlaender, head of Roche Molecular Diagnostics.

Photo by Daniel Gay

A group of scientists and activists are calling on the World Health Organization (WHO) to fight the spread of human T-cell leukemia virus subtype 1 (HTLV-1).

The group has written a letter to the WHO highlighting the global prevalence of HTLV-1 infection and recommending strategies to prevent the transmission of HTLV-1.

An abbreviated version of the letter was published in The Lancet. The full letter is available on the Global Virus Network (GVN)* website.

“Since my colleagues and I discovered HTLV-1 . . ., we have learned that this destructive and lethal virus is causing much devastation in communities with high prevalence,” said Robert C. Gallo, MD, co-founder and director of GVN and a professor at the University of Maryland School of Medicine in Baltimore.

“During the GVN meeting last September, I was astounded to learn of the hyper-endemic numbers in the Aboriginal population of Australia. HTLV-1 is endemic in other regions, including several islands of the Caribbean, and in countries such as Brazil, Iran, Japan, and Peru. We hope that the WHO will agree with us and begin to take action in promoting prevention strategies against HTLV-1.”

HTLV-1 prevalence

In their letter, Dr Gallo and his colleagues cite statistics of HTLV-1 prevalence around the world.

The authors note that, in a hospital-based cohort study conducted in Central Australia, 33.6% of Indigenous people tested HTLV-1 positive, with the incidence rate reaching 48.5% in older men.

Research has suggested that, in Brazil, the HTLV-1 prevalence rate is 1.8% in the general population, 1.3% in blood donors in certain regions, and 1.05% in pregnant women.

It is estimated that nearly 1 million people are HTLV-1-positive in Japan, and 850,000 to 1.7 million people in Nigeria are infected with the virus.

In Gabon, the HTLV-1 prevalence in adults is believed to be 5% to 10%. And in Central African Republic, 7% of older, female Pygmies in the southern region were found to be infected with HTLV-1.

Studies have indicated that 6.1% of the general population in Jamaica is positive for HTLV-1, and other Caribbean islands have similar prevalence rates.

The authors note that HTLV-1 and -2 have also been detected in non-endemic areas due to migration and sexual transmission.

It is estimated that 20,000 to 30,000 people are infected with HTLV-1 in the UK, and 10,000 to 25,000 people are infected in metropolitan France.

Other estimates suggest that 266,000 people are infected with HTLV-1 or -2 in the US, and 3600 people with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) remain undiagnosed.

“The general neglect, globally, of the importance of HTLV-1 as a sexually transmitted infection that causes a range of debilitating inflammatory diseases does our patients, who request a sexual health screen, a disservice,” said Graham P. Taylor, MDMB, DSc, a professor at Imperial College London in the UK.

“It is also important to recognize the importance of mother-to-child transmission of HTLV-1 in the development of adult T-cell leukemia/lymphoma (ATLL) decades later. Despite the availability of highly sensitive and specific diagnostic tests for infection and a proven intervention, except for Japan, there are no antenatal screening programs. Evaluating the cost-effectiveness of such programs should now be a priority.”

“To prevent mother-to-child infection, the Japanese government has been offering HTLV-1 screening for all pregnant women without cost,” noted Yoshi Yamano, MD, PhD, a professor at St. Marianna University School of Medicine in Kawasaki, Japan.

“Taking a leadership role to promote research, it also provides grants for clinical trials and patient registries focused on ATLL and HAM/TSP.”

Preventing transmission

The letter outlines 5 strategies to prevent or reduce transmission of HTLV-1. The authors recommend:

1. Protecting the sexually active population with routine HTLV-1 testing in sexual health clinics and through promotion of CMPC—Counsel & Monitor HTLV-1-positive patients, notify Partners, and promote Condom usage
2. Protecting blood and organ donors and recipients by testing for HTLV, avoiding use of products that may be infected, and promoting CMPC
3. Protecting mothers, babies, and fathers via routine antenatal care testing, advising HTLV-1-positive mothers against breastfeeding (when feasible), and promoting CMPC
4. Protecting injectable drug users by promoting HTLV-1 testing, providing safe needles through needle exchange program, and promoting CMPC
5. Supporting the general population and healthcare providers by providing access to an up-to-date WHO HTLV-1 Fact Sheet that can help healthcare providers diagnose HTLV-1 and related diseases and help patients protect themselves from HTLV-1.

“This virus has been underestimated since the time of its discovery perhaps because it is restricted to certain regions or because it is not terribly infectious,” said William Hall, MD, PhD, co-founder of GVN and a professor at the University College Dublin in Ireland.

“However, for decades, it has been known that HTLV-1 is highly carcinogenic and causes severe paralytic neurologic disease and immune disorders that can lead to bacterial infections. It is time that the WHO publicize prevention strategies against this devastating virus.”

*GVN is an international coalition of medical virologists dedicated to identifying, researching, fighting, and preventing current and emerging pandemic viruses that pose a threat to public health.

Photo by Daniel Gay

A group of scientists and activists are calling on the World Health Organization (WHO) to fight the spread of human T-cell leukemia virus subtype 1 (HTLV-1).

The group has written a letter to the WHO highlighting the global prevalence of HTLV-1 infection and recommending strategies to prevent the transmission of HTLV-1.

An abbreviated version of the letter was published in The Lancet. The full letter is available on the Global Virus Network (GVN)* website.

“Since my colleagues and I discovered HTLV-1 . . ., we have learned that this destructive and lethal virus is causing much devastation in communities with high prevalence,” said Robert C. Gallo, MD, co-founder and director of GVN and a professor at the University of Maryland School of Medicine in Baltimore.

“During the GVN meeting last September, I was astounded to learn of the hyper-endemic numbers in the Aboriginal population of Australia. HTLV-1 is endemic in other regions, including several islands of the Caribbean, and in countries such as Brazil, Iran, Japan, and Peru. We hope that the WHO will agree with us and begin to take action in promoting prevention strategies against HTLV-1.”

HTLV-1 prevalence

In their letter, Dr Gallo and his colleagues cite statistics of HTLV-1 prevalence around the world.

The authors note that, in a hospital-based cohort study conducted in Central Australia, 33.6% of Indigenous people tested HTLV-1 positive, with the incidence rate reaching 48.5% in older men.

Research has suggested that, in Brazil, the HTLV-1 prevalence rate is 1.8% in the general population, 1.3% in blood donors in certain regions, and 1.05% in pregnant women.

It is estimated that nearly 1 million people are HTLV-1-positive in Japan, and 850,000 to 1.7 million people in Nigeria are infected with the virus.

In Gabon, the HTLV-1 prevalence in adults is believed to be 5% to 10%. And in Central African Republic, 7% of older, female Pygmies in the southern region were found to be infected with HTLV-1.

Studies have indicated that 6.1% of the general population in Jamaica is positive for HTLV-1, and other Caribbean islands have similar prevalence rates.

The authors note that HTLV-1 and -2 have also been detected in non-endemic areas due to migration and sexual transmission.

It is estimated that 20,000 to 30,000 people are infected with HTLV-1 in the UK, and 10,000 to 25,000 people are infected in metropolitan France.

Other estimates suggest that 266,000 people are infected with HTLV-1 or -2 in the US, and 3600 people with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) remain undiagnosed.

“The general neglect, globally, of the importance of HTLV-1 as a sexually transmitted infection that causes a range of debilitating inflammatory diseases does our patients, who request a sexual health screen, a disservice,” said Graham P. Taylor, MDMB, DSc, a professor at Imperial College London in the UK.

“It is also important to recognize the importance of mother-to-child transmission of HTLV-1 in the development of adult T-cell leukemia/lymphoma (ATLL) decades later. Despite the availability of highly sensitive and specific diagnostic tests for infection and a proven intervention, except for Japan, there are no antenatal screening programs. Evaluating the cost-effectiveness of such programs should now be a priority.”

“To prevent mother-to-child infection, the Japanese government has been offering HTLV-1 screening for all pregnant women without cost,” noted Yoshi Yamano, MD, PhD, a professor at St. Marianna University School of Medicine in Kawasaki, Japan.

“Taking a leadership role to promote research, it also provides grants for clinical trials and patient registries focused on ATLL and HAM/TSP.”

Preventing transmission

The letter outlines 5 strategies to prevent or reduce transmission of HTLV-1. The authors recommend:

1. Protecting the sexually active population with routine HTLV-1 testing in sexual health clinics and through promotion of CMPC—Counsel & Monitor HTLV-1-positive patients, notify Partners, and promote Condom usage
2. Protecting blood and organ donors and recipients by testing for HTLV, avoiding use of products that may be infected, and promoting CMPC
3. Protecting mothers, babies, and fathers via routine antenatal care testing, advising HTLV-1-positive mothers against breastfeeding (when feasible), and promoting CMPC
4. Protecting injectable drug users by promoting HTLV-1 testing, providing safe needles through needle exchange program, and promoting CMPC
5. Supporting the general population and healthcare providers by providing access to an up-to-date WHO HTLV-1 Fact Sheet that can help healthcare providers diagnose HTLV-1 and related diseases and help patients protect themselves from HTLV-1.

“This virus has been underestimated since the time of its discovery perhaps because it is restricted to certain regions or because it is not terribly infectious,” said William Hall, MD, PhD, co-founder of GVN and a professor at the University College Dublin in Ireland.

“However, for decades, it has been known that HTLV-1 is highly carcinogenic and causes severe paralytic neurologic disease and immune disorders that can lead to bacterial infections. It is time that the WHO publicize prevention strategies against this devastating virus.”

*GVN is an international coalition of medical virologists dedicated to identifying, researching, fighting, and preventing current and emerging pandemic viruses that pose a threat to public health.

Photo by Daniel Gay

A group of scientists and activists are calling on the World Health Organization (WHO) to fight the spread of human T-cell leukemia virus subtype 1 (HTLV-1).

The group has written a letter to the WHO highlighting the global prevalence of HTLV-1 infection and recommending strategies to prevent the transmission of HTLV-1.

An abbreviated version of the letter was published in The Lancet. The full letter is available on the Global Virus Network (GVN)* website.

“Since my colleagues and I discovered HTLV-1 . . ., we have learned that this destructive and lethal virus is causing much devastation in communities with high prevalence,” said Robert C. Gallo, MD, co-founder and director of GVN and a professor at the University of Maryland School of Medicine in Baltimore.

“During the GVN meeting last September, I was astounded to learn of the hyper-endemic numbers in the Aboriginal population of Australia. HTLV-1 is endemic in other regions, including several islands of the Caribbean, and in countries such as Brazil, Iran, Japan, and Peru. We hope that the WHO will agree with us and begin to take action in promoting prevention strategies against HTLV-1.”

HTLV-1 prevalence

In their letter, Dr Gallo and his colleagues cite statistics of HTLV-1 prevalence around the world.

The authors note that, in a hospital-based cohort study conducted in Central Australia, 33.6% of Indigenous people tested HTLV-1 positive, with the incidence rate reaching 48.5% in older men.

Research has suggested that, in Brazil, the HTLV-1 prevalence rate is 1.8% in the general population, 1.3% in blood donors in certain regions, and 1.05% in pregnant women.

It is estimated that nearly 1 million people are HTLV-1-positive in Japan, and 850,000 to 1.7 million people in Nigeria are infected with the virus.

In Gabon, the HTLV-1 prevalence in adults is believed to be 5% to 10%. And in Central African Republic, 7% of older, female Pygmies in the southern region were found to be infected with HTLV-1.

Studies have indicated that 6.1% of the general population in Jamaica is positive for HTLV-1, and other Caribbean islands have similar prevalence rates.

The authors note that HTLV-1 and -2 have also been detected in non-endemic areas due to migration and sexual transmission.

It is estimated that 20,000 to 30,000 people are infected with HTLV-1 in the UK, and 10,000 to 25,000 people are infected in metropolitan France.

Other estimates suggest that 266,000 people are infected with HTLV-1 or -2 in the US, and 3600 people with HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) remain undiagnosed.

“The general neglect, globally, of the importance of HTLV-1 as a sexually transmitted infection that causes a range of debilitating inflammatory diseases does our patients, who request a sexual health screen, a disservice,” said Graham P. Taylor, MDMB, DSc, a professor at Imperial College London in the UK.

“It is also important to recognize the importance of mother-to-child transmission of HTLV-1 in the development of adult T-cell leukemia/lymphoma (ATLL) decades later. Despite the availability of highly sensitive and specific diagnostic tests for infection and a proven intervention, except for Japan, there are no antenatal screening programs. Evaluating the cost-effectiveness of such programs should now be a priority.”

“To prevent mother-to-child infection, the Japanese government has been offering HTLV-1 screening for all pregnant women without cost,” noted Yoshi Yamano, MD, PhD, a professor at St. Marianna University School of Medicine in Kawasaki, Japan.

“Taking a leadership role to promote research, it also provides grants for clinical trials and patient registries focused on ATLL and HAM/TSP.”

Preventing transmission

The letter outlines 5 strategies to prevent or reduce transmission of HTLV-1. The authors recommend:

1. Protecting the sexually active population with routine HTLV-1 testing in sexual health clinics and through promotion of CMPC—Counsel & Monitor HTLV-1-positive patients, notify Partners, and promote Condom usage
2. Protecting blood and organ donors and recipients by testing for HTLV, avoiding use of products that may be infected, and promoting CMPC
3. Protecting mothers, babies, and fathers via routine antenatal care testing, advising HTLV-1-positive mothers against breastfeeding (when feasible), and promoting CMPC
4. Protecting injectable drug users by promoting HTLV-1 testing, providing safe needles through needle exchange program, and promoting CMPC
5. Supporting the general population and healthcare providers by providing access to an up-to-date WHO HTLV-1 Fact Sheet that can help healthcare providers diagnose HTLV-1 and related diseases and help patients protect themselves from HTLV-1.

“This virus has been underestimated since the time of its discovery perhaps because it is restricted to certain regions or because it is not terribly infectious,” said William Hall, MD, PhD, co-founder of GVN and a professor at the University College Dublin in Ireland.

“However, for decades, it has been known that HTLV-1 is highly carcinogenic and causes severe paralytic neurologic disease and immune disorders that can lead to bacterial infections. It is time that the WHO publicize prevention strategies against this devastating virus.”

*GVN is an international coalition of medical virologists dedicated to identifying, researching, fighting, and preventing current and emerging pandemic viruses that pose a threat to public health.

Red blood cells

Researchers say they have found a way to generate customized red blood cells (RBCs) that might one day be used to avoid transfusion incompatibilities.

The team used genome editing to modify an erythroblast cell line, making it deficient in antigens responsible for common transfusion incompatibilities.

The cells in this line could then be differentiated to generate RBCs with broad transfusion compatibility.

The researchers stressed that many obstacles must be overcome before this approach can be translated to a clinical product. However, this work does demonstrate proof of principle.

Ashley Mark Toye, PhD, of the University of Bristol in Bristol, UK, and his colleagues described this work in EMBO Molecular Medicine.

With previous work, Dr Toye and his colleagues generated an immortalized human erythroblast cell line known as the Bristol Erythroid Line Adult (BEL-A). The team showed that this cell line can be induced to generate RBCs in the lab.

With the current study, the researchers engineered BEL-A to express fewer antigens and therefore be less immunogenic.

The team first conducted a 15-month survey in England to investigate which antigens most commonly caused challenges in identifying a matched donated unit for transfusion recipients. The survey revealed 56 patients who had rare blood types with alloantibodies against RBC antigens.

Twenty-two of the patients had alloantibodies to antigens located on glycophorin B (GPB), U, S, or s. Nineteen patients had alloantibodies to antigens within the Rh blood group system.

Ten patients had alloantibodies to the Duffy blood group, and 2 previously untransfused patients had Fy (a^-b^-). Ten patients had Kell antigen alloantibodies. Eight patients had the Bombay or para-Bombay phenotype. And 3 patients each had alloantibodies to Lu and Kidd antigens.

To create compatible RBCs, the researchers first removed these blood groups from BEL-A using CRISPR-Cas9 genome editing.

The team created several new cell lines that lacked individual blood groups before creating a single cell line in which the 5 most common blood groups were removed—ABO (Bombay phenotype), Rh (Rh_null), Kell (K₀), Duffy (Duffy_null), and GPB (S^-s^-U^-).

RBCs derived from this modified cell line could, theoretically, serve most of the challenging cases the researchers identified.

“Blood made using genetically edited cells could one day provide compatible transfusions for a group of patients for whom blood matching is difficult or impossible to achieve within the donor population,” Dr Toye said. “However, much more work will still be needed to produce blood cells suitable for patient use.”

Red blood cells

Researchers say they have found a way to generate customized red blood cells (RBCs) that might one day be used to avoid transfusion incompatibilities.

The team used genome editing to modify an erythroblast cell line, making it deficient in antigens responsible for common transfusion incompatibilities.

The cells in this line could then be differentiated to generate RBCs with broad transfusion compatibility.

The researchers stressed that many obstacles must be overcome before this approach can be translated to a clinical product. However, this work does demonstrate proof of principle.

Ashley Mark Toye, PhD, of the University of Bristol in Bristol, UK, and his colleagues described this work in EMBO Molecular Medicine.

With previous work, Dr Toye and his colleagues generated an immortalized human erythroblast cell line known as the Bristol Erythroid Line Adult (BEL-A). The team showed that this cell line can be induced to generate RBCs in the lab.

With the current study, the researchers engineered BEL-A to express fewer antigens and therefore be less immunogenic.

The team first conducted a 15-month survey in England to investigate which antigens most commonly caused challenges in identifying a matched donated unit for transfusion recipients. The survey revealed 56 patients who had rare blood types with alloantibodies against RBC antigens.

Twenty-two of the patients had alloantibodies to antigens located on glycophorin B (GPB), U, S, or s. Nineteen patients had alloantibodies to antigens within the Rh blood group system.

Ten patients had alloantibodies to the Duffy blood group, and 2 previously untransfused patients had Fy (a^-b^-). Ten patients had Kell antigen alloantibodies. Eight patients had the Bombay or para-Bombay phenotype. And 3 patients each had alloantibodies to Lu and Kidd antigens.

To create compatible RBCs, the researchers first removed these blood groups from BEL-A using CRISPR-Cas9 genome editing.

The team created several new cell lines that lacked individual blood groups before creating a single cell line in which the 5 most common blood groups were removed—ABO (Bombay phenotype), Rh (Rh_null), Kell (K₀), Duffy (Duffy_null), and GPB (S^-s^-U^-).

RBCs derived from this modified cell line could, theoretically, serve most of the challenging cases the researchers identified.

“Blood made using genetically edited cells could one day provide compatible transfusions for a group of patients for whom blood matching is difficult or impossible to achieve within the donor population,” Dr Toye said. “However, much more work will still be needed to produce blood cells suitable for patient use.”

Red blood cells

Researchers say they have found a way to generate customized red blood cells (RBCs) that might one day be used to avoid transfusion incompatibilities.

The team used genome editing to modify an erythroblast cell line, making it deficient in antigens responsible for common transfusion incompatibilities.

The cells in this line could then be differentiated to generate RBCs with broad transfusion compatibility.

The researchers stressed that many obstacles must be overcome before this approach can be translated to a clinical product. However, this work does demonstrate proof of principle.

Ashley Mark Toye, PhD, of the University of Bristol in Bristol, UK, and his colleagues described this work in EMBO Molecular Medicine.

With previous work, Dr Toye and his colleagues generated an immortalized human erythroblast cell line known as the Bristol Erythroid Line Adult (BEL-A). The team showed that this cell line can be induced to generate RBCs in the lab.

With the current study, the researchers engineered BEL-A to express fewer antigens and therefore be less immunogenic.

The team first conducted a 15-month survey in England to investigate which antigens most commonly caused challenges in identifying a matched donated unit for transfusion recipients. The survey revealed 56 patients who had rare blood types with alloantibodies against RBC antigens.

Twenty-two of the patients had alloantibodies to antigens located on glycophorin B (GPB), U, S, or s. Nineteen patients had alloantibodies to antigens within the Rh blood group system.

Ten patients had alloantibodies to the Duffy blood group, and 2 previously untransfused patients had Fy (a^-b^-). Ten patients had Kell antigen alloantibodies. Eight patients had the Bombay or para-Bombay phenotype. And 3 patients each had alloantibodies to Lu and Kidd antigens.

To create compatible RBCs, the researchers first removed these blood groups from BEL-A using CRISPR-Cas9 genome editing.

The team created several new cell lines that lacked individual blood groups before creating a single cell line in which the 5 most common blood groups were removed—ABO (Bombay phenotype), Rh (Rh_null), Kell (K₀), Duffy (Duffy_null), and GPB (S^-s^-U^-).

RBCs derived from this modified cell line could, theoretically, serve most of the challenging cases the researchers identified.

“Blood made using genetically edited cells could one day provide compatible transfusions for a group of patients for whom blood matching is difficult or impossible to achieve within the donor population,” Dr Toye said. “However, much more work will still be needed to produce blood cells suitable for patient use.”

Photo by Elise Amendola

Having type O blood is associated with high death rates in severe trauma patients, according to a study published in Critical Care.

Researchers found that severe trauma patients with type O blood had a death rate of 28%, compared to a rate of 11% in patients with other blood types.

“Loss of blood is the leading cause of death in patients with severe trauma, but studies on the association between different blood types and the risk of trauma death have been scarce,” said study author Wataru Takayama, of Tokyo Medical and Dental University Hospital of Medicine in Japan.

“We wanted to test the hypothesis that trauma survival is affected by differences in blood types.”

To do this, the researchers evaluated the medical records of 901 patients with severe trauma who had been transported to either of 2 tertiary emergency critical care medical centers in Japan from 2013 to 2016.

Most patients had type O (n=284, 32%) or type A blood (n=285, 32%), followed by type B (n=209, 23%) and type AB (n=123, 13%).

The mortality rate was significantly higher in patients with type O blood than in patients with the other blood types—28% and 11%, respectively (P<0.001).

In a multivariate analysis, mortality was significantly higher for patients with type O blood. The adjusted odds ratio was 2.86 (P<0.001).

Patients with type O blood have been shown to have lower levels of von Willebrand factor than patients with other blood types. The researchers suggested that a lower level of von Willebrand factor is a possible explanation for the higher death rate in trauma patients with blood type O.

“Our results also raise questions about how emergency transfusion of O type red blood cells to a severe trauma patient could affect homeostasis . . .  and if this is different from other blood types,” Dr Takayama said.

“Further research is necessary to investigate the results of our study and develop the best treatment strategy for severe trauma patients.”

In particular, further research is needed to determine if the findings from this study apply to other ethnic groups, as all the patients in this study were Japanese.

In addition, the researchers didn’t evaluate the impact of the individual blood types A, AB, or B on severe trauma death rates. They only compared type O to non-O blood types, which may have diluted the effect of individual blood types on patient survival.

Photo by Elise Amendola

Having type O blood is associated with high death rates in severe trauma patients, according to a study published in Critical Care.

Researchers found that severe trauma patients with type O blood had a death rate of 28%, compared to a rate of 11% in patients with other blood types.

“Loss of blood is the leading cause of death in patients with severe trauma, but studies on the association between different blood types and the risk of trauma death have been scarce,” said study author Wataru Takayama, of Tokyo Medical and Dental University Hospital of Medicine in Japan.

“We wanted to test the hypothesis that trauma survival is affected by differences in blood types.”

To do this, the researchers evaluated the medical records of 901 patients with severe trauma who had been transported to either of 2 tertiary emergency critical care medical centers in Japan from 2013 to 2016.

Most patients had type O (n=284, 32%) or type A blood (n=285, 32%), followed by type B (n=209, 23%) and type AB (n=123, 13%).

The mortality rate was significantly higher in patients with type O blood than in patients with the other blood types—28% and 11%, respectively (P<0.001).

In a multivariate analysis, mortality was significantly higher for patients with type O blood. The adjusted odds ratio was 2.86 (P<0.001).

Patients with type O blood have been shown to have lower levels of von Willebrand factor than patients with other blood types. The researchers suggested that a lower level of von Willebrand factor is a possible explanation for the higher death rate in trauma patients with blood type O.

“Our results also raise questions about how emergency transfusion of O type red blood cells to a severe trauma patient could affect homeostasis . . .  and if this is different from other blood types,” Dr Takayama said.

“Further research is necessary to investigate the results of our study and develop the best treatment strategy for severe trauma patients.”

In particular, further research is needed to determine if the findings from this study apply to other ethnic groups, as all the patients in this study were Japanese.

In addition, the researchers didn’t evaluate the impact of the individual blood types A, AB, or B on severe trauma death rates. They only compared type O to non-O blood types, which may have diluted the effect of individual blood types on patient survival.

Photo by Elise Amendola

Having type O blood is associated with high death rates in severe trauma patients, according to a study published in Critical Care.

Researchers found that severe trauma patients with type O blood had a death rate of 28%, compared to a rate of 11% in patients with other blood types.

“Loss of blood is the leading cause of death in patients with severe trauma, but studies on the association between different blood types and the risk of trauma death have been scarce,” said study author Wataru Takayama, of Tokyo Medical and Dental University Hospital of Medicine in Japan.

“We wanted to test the hypothesis that trauma survival is affected by differences in blood types.”

To do this, the researchers evaluated the medical records of 901 patients with severe trauma who had been transported to either of 2 tertiary emergency critical care medical centers in Japan from 2013 to 2016.

Most patients had type O (n=284, 32%) or type A blood (n=285, 32%), followed by type B (n=209, 23%) and type AB (n=123, 13%).

The mortality rate was significantly higher in patients with type O blood than in patients with the other blood types—28% and 11%, respectively (P<0.001).

In a multivariate analysis, mortality was significantly higher for patients with type O blood. The adjusted odds ratio was 2.86 (P<0.001).

Patients with type O blood have been shown to have lower levels of von Willebrand factor than patients with other blood types. The researchers suggested that a lower level of von Willebrand factor is a possible explanation for the higher death rate in trauma patients with blood type O.

“Our results also raise questions about how emergency transfusion of O type red blood cells to a severe trauma patient could affect homeostasis . . .  and if this is different from other blood types,” Dr Takayama said.

“Further research is necessary to investigate the results of our study and develop the best treatment strategy for severe trauma patients.”

In particular, further research is needed to determine if the findings from this study apply to other ethnic groups, as all the patients in this study were Japanese.

In addition, the researchers didn’t evaluate the impact of the individual blood types A, AB, or B on severe trauma death rates. They only compared type O to non-O blood types, which may have diluted the effect of individual blood types on patient survival.

Photo from Flickr

Health Canada has approved commercialization of the INTERCEPT Blood System for platelets, which is used for the ex vivo treatment and storage of platelet components.

The INTERCEPT Blood System for platelets can inactivate a range of pathogens—including viruses, bacteria, and protozoan parasites—to reduce the risk of transfusion-transmitted infections.

The system also inactivates contaminating donor leukocytes to reduce the risk of transfusion-associated graft-versus-host disease.

“[The INTERCEPT Blood System for platelets] provides an important, proactive safety measure to reduce the risk of transfusion-transmitted infections from known and emerging pathogens,” said Carol Moore, of Cerus Corporation, the company marketing the system.

“The approval provides blood centers the flexibility to pathogen-inactivate platelets derived from whole blood or apheresis collections, and stored in either platelet additive solution or plasma. In addition, Canadian blood centers will be able to create larger platelet pools from whole blood collections and use our double-dose INTERCEPT kits to yield 2 therapeutic platelet doses to realize improved operational efficiencies and economics.”

The INTERCEPT Blood System for platelets is Cerus Corporation’s second pathogen-inactivated system to be approved in Canada. The INTERCEPT Blood System for plasma was approved in May 2016.

The platelet and plasma systems use the same illumination device, the same active compound (amotosalen), and very similar production steps.

The INTERCEPT systems target a basic biological difference between the therapeutic components of blood. Platelets, plasma, and red blood cells do not require functional DNA or RNA for therapeutic efficacy. But pathogens and white blood cells do, in order to transmit infection.

The INTERCEPT systems use a proprietary molecule (amotosalen) that, when activated by UVA light, binds to and blocks the replication of DNA and RNA, preventing nucleic acid replication and rendering the pathogen inactive.

The INTERCEPT Blood System for platelets has been approved in Europe since 2002 and in the US since 2014.

Photo from Flickr

Health Canada has approved commercialization of the INTERCEPT Blood System for platelets, which is used for the ex vivo treatment and storage of platelet components.

The INTERCEPT Blood System for platelets can inactivate a range of pathogens—including viruses, bacteria, and protozoan parasites—to reduce the risk of transfusion-transmitted infections.

The system also inactivates contaminating donor leukocytes to reduce the risk of transfusion-associated graft-versus-host disease.

“[The INTERCEPT Blood System for platelets] provides an important, proactive safety measure to reduce the risk of transfusion-transmitted infections from known and emerging pathogens,” said Carol Moore, of Cerus Corporation, the company marketing the system.

“The approval provides blood centers the flexibility to pathogen-inactivate platelets derived from whole blood or apheresis collections, and stored in either platelet additive solution or plasma. In addition, Canadian blood centers will be able to create larger platelet pools from whole blood collections and use our double-dose INTERCEPT kits to yield 2 therapeutic platelet doses to realize improved operational efficiencies and economics.”

The INTERCEPT Blood System for platelets is Cerus Corporation’s second pathogen-inactivated system to be approved in Canada. The INTERCEPT Blood System for plasma was approved in May 2016.

The platelet and plasma systems use the same illumination device, the same active compound (amotosalen), and very similar production steps.

The INTERCEPT systems target a basic biological difference between the therapeutic components of blood. Platelets, plasma, and red blood cells do not require functional DNA or RNA for therapeutic efficacy. But pathogens and white blood cells do, in order to transmit infection.

The INTERCEPT systems use a proprietary molecule (amotosalen) that, when activated by UVA light, binds to and blocks the replication of DNA and RNA, preventing nucleic acid replication and rendering the pathogen inactive.

The INTERCEPT Blood System for platelets has been approved in Europe since 2002 and in the US since 2014.

Photo from Flickr

Health Canada has approved commercialization of the INTERCEPT Blood System for platelets, which is used for the ex vivo treatment and storage of platelet components.

The INTERCEPT Blood System for platelets can inactivate a range of pathogens—including viruses, bacteria, and protozoan parasites—to reduce the risk of transfusion-transmitted infections.

The system also inactivates contaminating donor leukocytes to reduce the risk of transfusion-associated graft-versus-host disease.

“[The INTERCEPT Blood System for platelets] provides an important, proactive safety measure to reduce the risk of transfusion-transmitted infections from known and emerging pathogens,” said Carol Moore, of Cerus Corporation, the company marketing the system.

“The approval provides blood centers the flexibility to pathogen-inactivate platelets derived from whole blood or apheresis collections, and stored in either platelet additive solution or plasma. In addition, Canadian blood centers will be able to create larger platelet pools from whole blood collections and use our double-dose INTERCEPT kits to yield 2 therapeutic platelet doses to realize improved operational efficiencies and economics.”

The INTERCEPT Blood System for platelets is Cerus Corporation’s second pathogen-inactivated system to be approved in Canada. The INTERCEPT Blood System for plasma was approved in May 2016.

The platelet and plasma systems use the same illumination device, the same active compound (amotosalen), and very similar production steps.

The INTERCEPT systems target a basic biological difference between the therapeutic components of blood. Platelets, plasma, and red blood cells do not require functional DNA or RNA for therapeutic efficacy. But pathogens and white blood cells do, in order to transmit infection.

The INTERCEPT systems use a proprietary molecule (amotosalen) that, when activated by UVA light, binds to and blocks the replication of DNA and RNA, preventing nucleic acid replication and rendering the pathogen inactive.

The INTERCEPT Blood System for platelets has been approved in Europe since 2002 and in the US since 2014.

Image from Andre E.X. Brown

Researchers say they have found a way to improve the coagulability of platelets—by loading them with thrombin encapsulated in liposomes.

Platelets modified in this way decreased clotting time and enhanced clot strength in blood samples from healthy subjects.

The platelets also reduced clotting time in samples from patients with hemophilia A and decreased thrombin generation time in samples from patients with trauma-induced coagulopathy (TIC).

“Coagulation, which depends on a series of complex biochemical reactions, works great for scrapes and paper cuts,” said study author Christian Kastrup, PhD, of the University of British Columbia in Vancouver, Canada.

“But trauma often overwhelms this intricate, delicate process. We wanted to make it more resilient.”

Dr Kastrup and his colleagues described this endeavor in the Journal of Thrombosis and Haemostasis.

The researchers inserted thrombin into nanoliposomes and mixed them with platelets. After the platelets absorbed the nanoparticles, the team immersed the cells in blood samples for testing.

In platelet-rich plasma (PRP), the clot initiation time was about 26% faster with the modified platelets than with normal platelets—8.8 ± 1.7 min and 11.9 ± 2.5 min, respectively. And the clot strength was about 16% greater—13.4 ± 1.7 kdyne cm^-1 and 11.5 ± 1.6 kdyne cm^-1, respectively.

In whole blood, the clot initiation time was about 13% faster with modified platelets than with normal platelets—11.2 ± 1.2 min and 12.9 ± 1.2 min, respectively. And the clot strength was about 22% greater—5.0 ± 0.6 kdyne cm^-1 and 4.1 ± 0.4 kdyne cm^-1, respectively.

The researchers also found the modified platelets offset the effect of acidosis. Acidifying PRP increased thrombin generation time by 1.0 (± 0.4) min, but the modified platelets decreased thrombin generation time by 1.6 (± 0.2) min.

The modified platelets lessened the effects of antiplatelet agents as well. Aspirin or naproxen slowed thrombin generation time by 1.3 (± 0.5) min.

However, the modified platelets generated thrombin 0.4 (± 0.4) min faster in the presence of aspirin and 0.6 (± 0.4) min faster in the presence of naproxen, compared to normal platelets.

The researchers also tested the modified platelets in samples from patients with hemophilia A. Normal PRP had a clot initiation time of 5.3 (± 0.5) min, and clotting time for hemophilia A PRP was 33% slower.

In the presence of the modified platelets, clotting time was 17% slower in hemophilia A PRP than in normal PRP.

Finally, the researchers tested the modified platelets in plasma from 2 patients with TIC. With normal platelets, thrombin generation times were 5.0 (± 0.1) min and 6.7 (± 0.2) min.

With the modified platelets, thrombin generation times decreased to 3.9 (± 0.1) min and 5.9 (± 0.1) min, respectively.

If these modified platelets prove effective in subsequent preclinical and clinical testing, Dr Kastrup envisions that trauma centers could have bags of plasma containing modified platelets on hand for patients with severe bleeding. The modification could conceivably be done at the time donated blood is processed.

“Trauma is the leading killer of people under 45 years old, and blood loss is the second most common cause of such deaths,” Dr Kastrup noted. “By tweaking the body’s own clotting mechanism, we might be able to make trauma more survivable.”

Image from Andre E.X. Brown

Researchers say they have found a way to improve the coagulability of platelets—by loading them with thrombin encapsulated in liposomes.

Platelets modified in this way decreased clotting time and enhanced clot strength in blood samples from healthy subjects.

The platelets also reduced clotting time in samples from patients with hemophilia A and decreased thrombin generation time in samples from patients with trauma-induced coagulopathy (TIC).

“Coagulation, which depends on a series of complex biochemical reactions, works great for scrapes and paper cuts,” said study author Christian Kastrup, PhD, of the University of British Columbia in Vancouver, Canada.

“But trauma often overwhelms this intricate, delicate process. We wanted to make it more resilient.”

Dr Kastrup and his colleagues described this endeavor in the Journal of Thrombosis and Haemostasis.

The researchers inserted thrombin into nanoliposomes and mixed them with platelets. After the platelets absorbed the nanoparticles, the team immersed the cells in blood samples for testing.

In platelet-rich plasma (PRP), the clot initiation time was about 26% faster with the modified platelets than with normal platelets—8.8 ± 1.7 min and 11.9 ± 2.5 min, respectively. And the clot strength was about 16% greater—13.4 ± 1.7 kdyne cm^-1 and 11.5 ± 1.6 kdyne cm^-1, respectively.

In whole blood, the clot initiation time was about 13% faster with modified platelets than with normal platelets—11.2 ± 1.2 min and 12.9 ± 1.2 min, respectively. And the clot strength was about 22% greater—5.0 ± 0.6 kdyne cm^-1 and 4.1 ± 0.4 kdyne cm^-1, respectively.

The researchers also found the modified platelets offset the effect of acidosis. Acidifying PRP increased thrombin generation time by 1.0 (± 0.4) min, but the modified platelets decreased thrombin generation time by 1.6 (± 0.2) min.

The modified platelets lessened the effects of antiplatelet agents as well. Aspirin or naproxen slowed thrombin generation time by 1.3 (± 0.5) min.

However, the modified platelets generated thrombin 0.4 (± 0.4) min faster in the presence of aspirin and 0.6 (± 0.4) min faster in the presence of naproxen, compared to normal platelets.

The researchers also tested the modified platelets in samples from patients with hemophilia A. Normal PRP had a clot initiation time of 5.3 (± 0.5) min, and clotting time for hemophilia A PRP was 33% slower.

In the presence of the modified platelets, clotting time was 17% slower in hemophilia A PRP than in normal PRP.

Finally, the researchers tested the modified platelets in plasma from 2 patients with TIC. With normal platelets, thrombin generation times were 5.0 (± 0.1) min and 6.7 (± 0.2) min.

With the modified platelets, thrombin generation times decreased to 3.9 (± 0.1) min and 5.9 (± 0.1) min, respectively.

If these modified platelets prove effective in subsequent preclinical and clinical testing, Dr Kastrup envisions that trauma centers could have bags of plasma containing modified platelets on hand for patients with severe bleeding. The modification could conceivably be done at the time donated blood is processed.

“Trauma is the leading killer of people under 45 years old, and blood loss is the second most common cause of such deaths,” Dr Kastrup noted. “By tweaking the body’s own clotting mechanism, we might be able to make trauma more survivable.”

Image from Andre E.X. Brown

Researchers say they have found a way to improve the coagulability of platelets—by loading them with thrombin encapsulated in liposomes.

Platelets modified in this way decreased clotting time and enhanced clot strength in blood samples from healthy subjects.

The platelets also reduced clotting time in samples from patients with hemophilia A and decreased thrombin generation time in samples from patients with trauma-induced coagulopathy (TIC).

“Coagulation, which depends on a series of complex biochemical reactions, works great for scrapes and paper cuts,” said study author Christian Kastrup, PhD, of the University of British Columbia in Vancouver, Canada.

“But trauma often overwhelms this intricate, delicate process. We wanted to make it more resilient.”

Dr Kastrup and his colleagues described this endeavor in the Journal of Thrombosis and Haemostasis.

The researchers inserted thrombin into nanoliposomes and mixed them with platelets. After the platelets absorbed the nanoparticles, the team immersed the cells in blood samples for testing.

In platelet-rich plasma (PRP), the clot initiation time was about 26% faster with the modified platelets than with normal platelets—8.8 ± 1.7 min and 11.9 ± 2.5 min, respectively. And the clot strength was about 16% greater—13.4 ± 1.7 kdyne cm^-1 and 11.5 ± 1.6 kdyne cm^-1, respectively.

In whole blood, the clot initiation time was about 13% faster with modified platelets than with normal platelets—11.2 ± 1.2 min and 12.9 ± 1.2 min, respectively. And the clot strength was about 22% greater—5.0 ± 0.6 kdyne cm^-1 and 4.1 ± 0.4 kdyne cm^-1, respectively.

The researchers also found the modified platelets offset the effect of acidosis. Acidifying PRP increased thrombin generation time by 1.0 (± 0.4) min, but the modified platelets decreased thrombin generation time by 1.6 (± 0.2) min.

The modified platelets lessened the effects of antiplatelet agents as well. Aspirin or naproxen slowed thrombin generation time by 1.3 (± 0.5) min.

However, the modified platelets generated thrombin 0.4 (± 0.4) min faster in the presence of aspirin and 0.6 (± 0.4) min faster in the presence of naproxen, compared to normal platelets.

The researchers also tested the modified platelets in samples from patients with hemophilia A. Normal PRP had a clot initiation time of 5.3 (± 0.5) min, and clotting time for hemophilia A PRP was 33% slower.

In the presence of the modified platelets, clotting time was 17% slower in hemophilia A PRP than in normal PRP.

Finally, the researchers tested the modified platelets in plasma from 2 patients with TIC. With normal platelets, thrombin generation times were 5.0 (± 0.1) min and 6.7 (± 0.2) min.

With the modified platelets, thrombin generation times decreased to 3.9 (± 0.1) min and 5.9 (± 0.1) min, respectively.

If these modified platelets prove effective in subsequent preclinical and clinical testing, Dr Kastrup envisions that trauma centers could have bags of plasma containing modified platelets on hand for patients with severe bleeding. The modification could conceivably be done at the time donated blood is processed.

“Trauma is the leading killer of people under 45 years old, and blood loss is the second most common cause of such deaths,” Dr Kastrup noted. “By tweaking the body’s own clotting mechanism, we might be able to make trauma more survivable.”

Photo by Darren Baker

The US Food and Drug Administration (FDA) has granted 510(k) clearance for ORTHO CONNECT V2.0, a software system developed by Ortho Clinical Diagnostics.

ORTHO CONNECT V2.0 is middleware designed to keep large quantities of data accessible and consistent across multiple instruments and laboratory systems.

ORTHO CONNECT V2.0 works with other products Ortho Clinical Diagnostics has developed for immunohematology labs.

The software is now available for purchase in the US.

According to Ortho Clinical Diagnostics, ORTHO CONNECT V2.0 is comprehensive, integrated, and customizable middleware (software that acts as a bridge between an operating system or database and application).

ORTHO CONNECT V2.0 centralizes laboratory operations and workflow across hospitals and networks, allowing blood banks and their data to be managed through one central terminal. The software can link all Ortho Clinical Diagnostics instruments to lab information systems through a single interface.

Acting as an intermediary between instruments and lab information systems, ORTHO CONNECT V2.0 allows labs to exchange data, perform data management, and complete regulatory process tasks that are not easily performed alone. All test results on connected analyzers can be viewed and verified no matter the location.

ORTHO CONNECT V2.0 enables the ORTHO VISION® and ORTHO VISION® Max immunohematology analyzers, which test blood for transfusion compatibility, to integrate with a hospital’s laboratory information systems through a single validated connection to exchange data and simplify processes.

“Ortho [Clinical Diagnostics] is focused on diminishing the complexities of immunohematology testing while improving safety, speed, and efficiency throughout the blood bank,” said Robert Yates, the company’s chief operating officer.

“ORTHO CONNECT does just that, bringing improved functionality to laboratory information systems that are often relatively rigid and outdated. It’s the perfect complement to our ORTHO VISION platform of analyzers.”

Photo by Darren Baker

The US Food and Drug Administration (FDA) has granted 510(k) clearance for ORTHO CONNECT V2.0, a software system developed by Ortho Clinical Diagnostics.

ORTHO CONNECT V2.0 is middleware designed to keep large quantities of data accessible and consistent across multiple instruments and laboratory systems.

ORTHO CONNECT V2.0 works with other products Ortho Clinical Diagnostics has developed for immunohematology labs.

The software is now available for purchase in the US.

According to Ortho Clinical Diagnostics, ORTHO CONNECT V2.0 is comprehensive, integrated, and customizable middleware (software that acts as a bridge between an operating system or database and application).

ORTHO CONNECT V2.0 centralizes laboratory operations and workflow across hospitals and networks, allowing blood banks and their data to be managed through one central terminal. The software can link all Ortho Clinical Diagnostics instruments to lab information systems through a single interface.

Acting as an intermediary between instruments and lab information systems, ORTHO CONNECT V2.0 allows labs to exchange data, perform data management, and complete regulatory process tasks that are not easily performed alone. All test results on connected analyzers can be viewed and verified no matter the location.

ORTHO CONNECT V2.0 enables the ORTHO VISION® and ORTHO VISION® Max immunohematology analyzers, which test blood for transfusion compatibility, to integrate with a hospital’s laboratory information systems through a single validated connection to exchange data and simplify processes.

“Ortho [Clinical Diagnostics] is focused on diminishing the complexities of immunohematology testing while improving safety, speed, and efficiency throughout the blood bank,” said Robert Yates, the company’s chief operating officer.

“ORTHO CONNECT does just that, bringing improved functionality to laboratory information systems that are often relatively rigid and outdated. It’s the perfect complement to our ORTHO VISION platform of analyzers.”

Photo by Darren Baker

The US Food and Drug Administration (FDA) has granted 510(k) clearance for ORTHO CONNECT V2.0, a software system developed by Ortho Clinical Diagnostics.

ORTHO CONNECT V2.0 is middleware designed to keep large quantities of data accessible and consistent across multiple instruments and laboratory systems.

ORTHO CONNECT V2.0 works with other products Ortho Clinical Diagnostics has developed for immunohematology labs.

The software is now available for purchase in the US.

According to Ortho Clinical Diagnostics, ORTHO CONNECT V2.0 is comprehensive, integrated, and customizable middleware (software that acts as a bridge between an operating system or database and application).

ORTHO CONNECT V2.0 centralizes laboratory operations and workflow across hospitals and networks, allowing blood banks and their data to be managed through one central terminal. The software can link all Ortho Clinical Diagnostics instruments to lab information systems through a single interface.

Acting as an intermediary between instruments and lab information systems, ORTHO CONNECT V2.0 allows labs to exchange data, perform data management, and complete regulatory process tasks that are not easily performed alone. All test results on connected analyzers can be viewed and verified no matter the location.

ORTHO CONNECT V2.0 enables the ORTHO VISION® and ORTHO VISION® Max immunohematology analyzers, which test blood for transfusion compatibility, to integrate with a hospital’s laboratory information systems through a single validated connection to exchange data and simplify processes.

“Ortho [Clinical Diagnostics] is focused on diminishing the complexities of immunohematology testing while improving safety, speed, and efficiency throughout the blood bank,” said Robert Yates, the company’s chief operating officer.

“ORTHO CONNECT does just that, bringing improved functionality to laboratory information systems that are often relatively rigid and outdated. It’s the perfect complement to our ORTHO VISION platform of analyzers.”

of Alabama at Birmingham

Free heme plays a key role in the adverse effects associated with massive transfusion of stored red blood cells (RBCs), according to researchers.

Experiments in a mouse model of trauma hemorrhage revealed a greater risk of mortality from bacterial pneumonia in mice that received transfusions of blood stored for 14 days, rather than fresh blood.

This greater risk was dependent upon free heme, which is released from RBCs during storage and upon transfusion.

In a study of human trauma patients, researchers found the amount of heme was proportional to the amount of blood transfused.

Brant M. Wagener, MD, PhD, of University of Alabama at Birmingham, and his colleagues detailed these findings in PLOS Medicine.

In the mouse model of trauma hemorrhage, the researchers resuscitated mice using either fresh blood (stored for 0 days) or blood stored for 2 weeks. (A 2-week storage of mouse blood approximates storage of human RBCs for 42 days.)

Two days after transfusion, the mice were challenged by instilling the lungs with the bacteria Pseudomonas aeruginosa.

Mice that received the stored blood had a significant increase in bacterial lung injury, as shown by higher mortality, and increased fluid accumulation and bacterial numbers in the lungs.

The researchers identified the connection between free heme and infection susceptibility/severity in 2 ways.

First, Pseudomonas aeruginosa-induced mortality was completely prevented by the addition of hemopexin, a scavenging protein that removes free heme from the blood.

Second, adding an inhibitor of toll-like receptor 4 (TLR4), or genetically removing TLR4 from mice, also prevented bacteria-induced mortality. Free heme—which is known to induce inflammatory injury to major organs in diseases like sickle cell or sepsis—acts, in part, by activating TLR4.

The researchers also found that transfusion with stored blood induced release of the inflammation mediator high mobility group box 1 (HMGB1). But an anti-HMGB1 antibody protected mice from bacteria-induced mortality.

The anti-HMGB1 antibody also restored macrophage-dependent phagocytosis of Pseudomonas aeruginosa in vitro.

Tissue culture experiments had revealed that free heme inhibits macrophages from ingesting Pseudomonas aeruginosa, and the addition of free heme increases permeability in endothelial cells.

Finally, in a 16-month study, the researchers found that human trauma-hemorrhage patients who received large amounts of transfused blood were also receiving amounts of free heme sufficient to overwhelm the normal amounts of hemopexin found in a person’s blood.

The researchers said this work underscores the need to confirm whether the storage age of transfused RBCs correlates with increasing levels of free heme after transfusion. The team would also like to establish whether patients with low ratios of hemopexin to free heme have a greater risk for adverse outcomes after massive transfusions.

of Alabama at Birmingham

Free heme plays a key role in the adverse effects associated with massive transfusion of stored red blood cells (RBCs), according to researchers.

Experiments in a mouse model of trauma hemorrhage revealed a greater risk of mortality from bacterial pneumonia in mice that received transfusions of blood stored for 14 days, rather than fresh blood.

This greater risk was dependent upon free heme, which is released from RBCs during storage and upon transfusion.

In a study of human trauma patients, researchers found the amount of heme was proportional to the amount of blood transfused.

Brant M. Wagener, MD, PhD, of University of Alabama at Birmingham, and his colleagues detailed these findings in PLOS Medicine.

In the mouse model of trauma hemorrhage, the researchers resuscitated mice using either fresh blood (stored for 0 days) or blood stored for 2 weeks. (A 2-week storage of mouse blood approximates storage of human RBCs for 42 days.)

Two days after transfusion, the mice were challenged by instilling the lungs with the bacteria Pseudomonas aeruginosa.

Mice that received the stored blood had a significant increase in bacterial lung injury, as shown by higher mortality, and increased fluid accumulation and bacterial numbers in the lungs.

The researchers identified the connection between free heme and infection susceptibility/severity in 2 ways.

First, Pseudomonas aeruginosa-induced mortality was completely prevented by the addition of hemopexin, a scavenging protein that removes free heme from the blood.

Second, adding an inhibitor of toll-like receptor 4 (TLR4), or genetically removing TLR4 from mice, also prevented bacteria-induced mortality. Free heme—which is known to induce inflammatory injury to major organs in diseases like sickle cell or sepsis—acts, in part, by activating TLR4.

The researchers also found that transfusion with stored blood induced release of the inflammation mediator high mobility group box 1 (HMGB1). But an anti-HMGB1 antibody protected mice from bacteria-induced mortality.

The anti-HMGB1 antibody also restored macrophage-dependent phagocytosis of Pseudomonas aeruginosa in vitro.

Tissue culture experiments had revealed that free heme inhibits macrophages from ingesting Pseudomonas aeruginosa, and the addition of free heme increases permeability in endothelial cells.

Finally, in a 16-month study, the researchers found that human trauma-hemorrhage patients who received large amounts of transfused blood were also receiving amounts of free heme sufficient to overwhelm the normal amounts of hemopexin found in a person’s blood.

The researchers said this work underscores the need to confirm whether the storage age of transfused RBCs correlates with increasing levels of free heme after transfusion. The team would also like to establish whether patients with low ratios of hemopexin to free heme have a greater risk for adverse outcomes after massive transfusions.

of Alabama at Birmingham

Free heme plays a key role in the adverse effects associated with massive transfusion of stored red blood cells (RBCs), according to researchers.

Experiments in a mouse model of trauma hemorrhage revealed a greater risk of mortality from bacterial pneumonia in mice that received transfusions of blood stored for 14 days, rather than fresh blood.

This greater risk was dependent upon free heme, which is released from RBCs during storage and upon transfusion.

In a study of human trauma patients, researchers found the amount of heme was proportional to the amount of blood transfused.

Brant M. Wagener, MD, PhD, of University of Alabama at Birmingham, and his colleagues detailed these findings in PLOS Medicine.

In the mouse model of trauma hemorrhage, the researchers resuscitated mice using either fresh blood (stored for 0 days) or blood stored for 2 weeks. (A 2-week storage of mouse blood approximates storage of human RBCs for 42 days.)

Two days after transfusion, the mice were challenged by instilling the lungs with the bacteria Pseudomonas aeruginosa.

Mice that received the stored blood had a significant increase in bacterial lung injury, as shown by higher mortality, and increased fluid accumulation and bacterial numbers in the lungs.

The researchers identified the connection between free heme and infection susceptibility/severity in 2 ways.

First, Pseudomonas aeruginosa-induced mortality was completely prevented by the addition of hemopexin, a scavenging protein that removes free heme from the blood.

Second, adding an inhibitor of toll-like receptor 4 (TLR4), or genetically removing TLR4 from mice, also prevented bacteria-induced mortality. Free heme—which is known to induce inflammatory injury to major organs in diseases like sickle cell or sepsis—acts, in part, by activating TLR4.

The researchers also found that transfusion with stored blood induced release of the inflammation mediator high mobility group box 1 (HMGB1). But an anti-HMGB1 antibody protected mice from bacteria-induced mortality.

The anti-HMGB1 antibody also restored macrophage-dependent phagocytosis of Pseudomonas aeruginosa in vitro.

Tissue culture experiments had revealed that free heme inhibits macrophages from ingesting Pseudomonas aeruginosa, and the addition of free heme increases permeability in endothelial cells.

Finally, in a 16-month study, the researchers found that human trauma-hemorrhage patients who received large amounts of transfused blood were also receiving amounts of free heme sufficient to overwhelm the normal amounts of hemopexin found in a person’s blood.

The researchers said this work underscores the need to confirm whether the storage age of transfused RBCs correlates with increasing levels of free heme after transfusion. The team would also like to establish whether patients with low ratios of hemopexin to free heme have a greater risk for adverse outcomes after massive transfusions.