Spray-dried plasma inches toward clinical trials

SAN DIEGO – Spray-dried plasma compared well with fresh frozen plasma in two in vitro studies, but clinical studies are needed to confirm the findings, researchers reported at the annual meeting of the American Association of Blood Banks.

The product’s logistical benefits include ease of transport, stability at room temperature, and the ability to be rapidly reconstituted – attributes that make it particularly useful in combat situations and prehospital settings where it is impractical to administer fresh frozen plasma (FFP).

The advantages of reconstituted blood products in combat settings have prompted recent efforts to speed their availability. The Food and Drug Administration and the Department of Defense recently announced a joint program to expedite the FDA’s review of products that could diagnose, treat, or prevent life-threatening conditions facing U.S. military personnel. It would be a fast-track process similar to how the FDA handles the breakthrough designation program.

In the first study, the investigators compared spray-dried plasma (SpDP) and FFP in reconstituted whole blood to test their hypothesis that SpDP is not inferior to FFP in facilitating platelet adhesion and thrombus formation, as evaluated by using a microfusion assay.

“Trauma is frequently associated with the use of plasma,” said Rachel S. Bercovitz, MD, MS, of the BloodCenter of Wisconsin and associate professor of pediatrics (hematology, oncology, and stem cell transplantation) at Northwestern University, Chicago.

Compared with FFP, SpDP can be reconstituted in 5 minutes and has more than 80% of the procoagulation and anticoagulation proteins, she explained. “Factor 8 levels were lower in the spray-dried plasma and were about at the 70% level of FFP. The other factor that was reduced, as compared to the FFP, was the von Willebrand factor (vWF), which was about 60% in SpDP compared to FFP.”

Whole blood was obtained from healthy volunteers and red blood cells (RBCs) were separated from platelet-rich plasma, and following standard procedures, resuspended in either SpDP or FFP and recombined with the packed red blood cells to create reconstituted whole blood with hematocrit of 34%-40% and 150,000-250,000 platelets per mcL.

After fluorescent labeling, the samples were flowed through a type I collagen-coated microchannel and still images of adherent platelets and thrombi were captured in order to calculate surface area coverage along the length of the channel. Next, the investigators used a ratio paired t-test to compare surface area coverage in SpDP versus FFP. The margin of noninferiority was 20% (SpDP/FFP greater than 0.8).

A total of six batches of SpDP and FFP were evaluated with 17 donors, and there was no statistical difference between the SpDP versus FFP pairs (P = .7558).

The mean ratio of SpDP versus FFP was 1.21 with a 95% confidence interval of 0.84-1.57. The surface area coverage in samples that were reconstituted with SpDP were, on average, 20% greater than in samples reconstituted with FFP. The lower limit of the 95% confidence interval was a difference of 16%, and therefore lower than the a priori determined margin of noninferiority of 20%.

“We found that SpDP is not inferior to FFP in supporting platelet adhesion and thrombus formation in our in vitro model,” Dr. Bercovitz said. “We feel that these in vitro assays support further in vivo studies of safety and efficacy of spray dried plasma.”

In a second study, Michael A. Meledeo, PhD, of the U.S. Army Institute of Surgical Research (coagulation and blood research), and his colleagues examined methods of reconstituting SpDP. They noted that a single unit process has been developed that produces a long-lived and readily stored SpDP product, which decreased high-molecular-weight multimers of vWF but increased low-molecular-weight multimers. vWF is critical in the process of platelet adhesion and thrombus formation, Dr. Meledeo said.

The researchers examined different reconstitution solutions: FFP, FFP with glycine, regular SpDP without pretreatment and rehydrated with glycine-hydrochloride:glycine, SpDP pretreated with glycine-HCl, or glycine-HCl:glycine and rehydrated with water.

Several in vitro analyses were performed, including measurement of vWF activity, fibrin polymerization kinetics, thrombin generation, coagulation properties and platelet adhesion to collagen.

Pretreated SpDP had better vWF activity, compared with regular SpDP (P less than .05). As compared with FFP, fibrin polymerization density was slightly lower in regular SpDP (0.879 vs. 0.742 optical density; P less than .01), although generation of thrombin was similar.

The researchers also found that the bicarbonate/base excess were lower in SpDP samples versus FFP (P less than .001). Thromboelastography results (used to measure coagulation properties) remained unchanged in plasma-only samples, but clot strength in reconstructed whole blood was reduced in all SpDP samples, compared with FFP (63.82 vs. 55-59.38; P less than .01).

Finally, platelet adhesion was equivalent in pretreated SpDP samples and FFP, while with regular SpDP, it was improved as compared with all other samples (71.53% surface coverage vs. 30.26%-43.87%; P less than .05).

“Based on these results, spray dried plasma was equivalent or superior to FFP in most of the in vitro hemostasis assays,” Dr. Meledeo said. “Reconstitution with glycine-HCl or glycine-HCl:glycine induced a superior von Willebrand function, but it was inferior in terms of supporting a flowing platelet adhesion to collagen.”

Dr. Bercovitz and Dr. Meledeo reported having no financial disclosures.

[email protected]

SOURCES: Bercovitz R et al. AABB 17 Abstract C20-A02B; Meledeo M et al. AABB 17 Abstract C21-A02B.

SAN DIEGO – Spray-dried plasma compared well with fresh frozen plasma in two in vitro studies, but clinical studies are needed to confirm the findings, researchers reported at the annual meeting of the American Association of Blood Banks.

The product’s logistical benefits include ease of transport, stability at room temperature, and the ability to be rapidly reconstituted – attributes that make it particularly useful in combat situations and prehospital settings where it is impractical to administer fresh frozen plasma (FFP).

The advantages of reconstituted blood products in combat settings have prompted recent efforts to speed their availability. The Food and Drug Administration and the Department of Defense recently announced a joint program to expedite the FDA’s review of products that could diagnose, treat, or prevent life-threatening conditions facing U.S. military personnel. It would be a fast-track process similar to how the FDA handles the breakthrough designation program.

In the first study, the investigators compared spray-dried plasma (SpDP) and FFP in reconstituted whole blood to test their hypothesis that SpDP is not inferior to FFP in facilitating platelet adhesion and thrombus formation, as evaluated by using a microfusion assay.

“Trauma is frequently associated with the use of plasma,” said Rachel S. Bercovitz, MD, MS, of the BloodCenter of Wisconsin and associate professor of pediatrics (hematology, oncology, and stem cell transplantation) at Northwestern University, Chicago.

Compared with FFP, SpDP can be reconstituted in 5 minutes and has more than 80% of the procoagulation and anticoagulation proteins, she explained. “Factor 8 levels were lower in the spray-dried plasma and were about at the 70% level of FFP. The other factor that was reduced, as compared to the FFP, was the von Willebrand factor (vWF), which was about 60% in SpDP compared to FFP.”

Whole blood was obtained from healthy volunteers and red blood cells (RBCs) were separated from platelet-rich plasma, and following standard procedures, resuspended in either SpDP or FFP and recombined with the packed red blood cells to create reconstituted whole blood with hematocrit of 34%-40% and 150,000-250,000 platelets per mcL.

After fluorescent labeling, the samples were flowed through a type I collagen-coated microchannel and still images of adherent platelets and thrombi were captured in order to calculate surface area coverage along the length of the channel. Next, the investigators used a ratio paired t-test to compare surface area coverage in SpDP versus FFP. The margin of noninferiority was 20% (SpDP/FFP greater than 0.8).

A total of six batches of SpDP and FFP were evaluated with 17 donors, and there was no statistical difference between the SpDP versus FFP pairs (P = .7558).

The mean ratio of SpDP versus FFP was 1.21 with a 95% confidence interval of 0.84-1.57. The surface area coverage in samples that were reconstituted with SpDP were, on average, 20% greater than in samples reconstituted with FFP. The lower limit of the 95% confidence interval was a difference of 16%, and therefore lower than the a priori determined margin of noninferiority of 20%.

“We found that SpDP is not inferior to FFP in supporting platelet adhesion and thrombus formation in our in vitro model,” Dr. Bercovitz said. “We feel that these in vitro assays support further in vivo studies of safety and efficacy of spray dried plasma.”

In a second study, Michael A. Meledeo, PhD, of the U.S. Army Institute of Surgical Research (coagulation and blood research), and his colleagues examined methods of reconstituting SpDP. They noted that a single unit process has been developed that produces a long-lived and readily stored SpDP product, which decreased high-molecular-weight multimers of vWF but increased low-molecular-weight multimers. vWF is critical in the process of platelet adhesion and thrombus formation, Dr. Meledeo said.

The researchers examined different reconstitution solutions: FFP, FFP with glycine, regular SpDP without pretreatment and rehydrated with glycine-hydrochloride:glycine, SpDP pretreated with glycine-HCl, or glycine-HCl:glycine and rehydrated with water.

Several in vitro analyses were performed, including measurement of vWF activity, fibrin polymerization kinetics, thrombin generation, coagulation properties and platelet adhesion to collagen.

Pretreated SpDP had better vWF activity, compared with regular SpDP (P less than .05). As compared with FFP, fibrin polymerization density was slightly lower in regular SpDP (0.879 vs. 0.742 optical density; P less than .01), although generation of thrombin was similar.

The researchers also found that the bicarbonate/base excess were lower in SpDP samples versus FFP (P less than .001). Thromboelastography results (used to measure coagulation properties) remained unchanged in plasma-only samples, but clot strength in reconstructed whole blood was reduced in all SpDP samples, compared with FFP (63.82 vs. 55-59.38; P less than .01).

Finally, platelet adhesion was equivalent in pretreated SpDP samples and FFP, while with regular SpDP, it was improved as compared with all other samples (71.53% surface coverage vs. 30.26%-43.87%; P less than .05).

“Based on these results, spray dried plasma was equivalent or superior to FFP in most of the in vitro hemostasis assays,” Dr. Meledeo said. “Reconstitution with glycine-HCl or glycine-HCl:glycine induced a superior von Willebrand function, but it was inferior in terms of supporting a flowing platelet adhesion to collagen.”

Dr. Bercovitz and Dr. Meledeo reported having no financial disclosures.

[email protected]

SOURCES: Bercovitz R et al. AABB 17 Abstract C20-A02B; Meledeo M et al. AABB 17 Abstract C21-A02B.

SAN DIEGO – Spray-dried plasma compared well with fresh frozen plasma in two in vitro studies, but clinical studies are needed to confirm the findings, researchers reported at the annual meeting of the American Association of Blood Banks.

The product’s logistical benefits include ease of transport, stability at room temperature, and the ability to be rapidly reconstituted – attributes that make it particularly useful in combat situations and prehospital settings where it is impractical to administer fresh frozen plasma (FFP).

The advantages of reconstituted blood products in combat settings have prompted recent efforts to speed their availability. The Food and Drug Administration and the Department of Defense recently announced a joint program to expedite the FDA’s review of products that could diagnose, treat, or prevent life-threatening conditions facing U.S. military personnel. It would be a fast-track process similar to how the FDA handles the breakthrough designation program.

In the first study, the investigators compared spray-dried plasma (SpDP) and FFP in reconstituted whole blood to test their hypothesis that SpDP is not inferior to FFP in facilitating platelet adhesion and thrombus formation, as evaluated by using a microfusion assay.

“Trauma is frequently associated with the use of plasma,” said Rachel S. Bercovitz, MD, MS, of the BloodCenter of Wisconsin and associate professor of pediatrics (hematology, oncology, and stem cell transplantation) at Northwestern University, Chicago.

Compared with FFP, SpDP can be reconstituted in 5 minutes and has more than 80% of the procoagulation and anticoagulation proteins, she explained. “Factor 8 levels were lower in the spray-dried plasma and were about at the 70% level of FFP. The other factor that was reduced, as compared to the FFP, was the von Willebrand factor (vWF), which was about 60% in SpDP compared to FFP.”

Whole blood was obtained from healthy volunteers and red blood cells (RBCs) were separated from platelet-rich plasma, and following standard procedures, resuspended in either SpDP or FFP and recombined with the packed red blood cells to create reconstituted whole blood with hematocrit of 34%-40% and 150,000-250,000 platelets per mcL.

After fluorescent labeling, the samples were flowed through a type I collagen-coated microchannel and still images of adherent platelets and thrombi were captured in order to calculate surface area coverage along the length of the channel. Next, the investigators used a ratio paired t-test to compare surface area coverage in SpDP versus FFP. The margin of noninferiority was 20% (SpDP/FFP greater than 0.8).

A total of six batches of SpDP and FFP were evaluated with 17 donors, and there was no statistical difference between the SpDP versus FFP pairs (P = .7558).

The mean ratio of SpDP versus FFP was 1.21 with a 95% confidence interval of 0.84-1.57. The surface area coverage in samples that were reconstituted with SpDP were, on average, 20% greater than in samples reconstituted with FFP. The lower limit of the 95% confidence interval was a difference of 16%, and therefore lower than the a priori determined margin of noninferiority of 20%.

“We found that SpDP is not inferior to FFP in supporting platelet adhesion and thrombus formation in our in vitro model,” Dr. Bercovitz said. “We feel that these in vitro assays support further in vivo studies of safety and efficacy of spray dried plasma.”

In a second study, Michael A. Meledeo, PhD, of the U.S. Army Institute of Surgical Research (coagulation and blood research), and his colleagues examined methods of reconstituting SpDP. They noted that a single unit process has been developed that produces a long-lived and readily stored SpDP product, which decreased high-molecular-weight multimers of vWF but increased low-molecular-weight multimers. vWF is critical in the process of platelet adhesion and thrombus formation, Dr. Meledeo said.

The researchers examined different reconstitution solutions: FFP, FFP with glycine, regular SpDP without pretreatment and rehydrated with glycine-hydrochloride:glycine, SpDP pretreated with glycine-HCl, or glycine-HCl:glycine and rehydrated with water.

Several in vitro analyses were performed, including measurement of vWF activity, fibrin polymerization kinetics, thrombin generation, coagulation properties and platelet adhesion to collagen.

Pretreated SpDP had better vWF activity, compared with regular SpDP (P less than .05). As compared with FFP, fibrin polymerization density was slightly lower in regular SpDP (0.879 vs. 0.742 optical density; P less than .01), although generation of thrombin was similar.

The researchers also found that the bicarbonate/base excess were lower in SpDP samples versus FFP (P less than .001). Thromboelastography results (used to measure coagulation properties) remained unchanged in plasma-only samples, but clot strength in reconstructed whole blood was reduced in all SpDP samples, compared with FFP (63.82 vs. 55-59.38; P less than .01).

Finally, platelet adhesion was equivalent in pretreated SpDP samples and FFP, while with regular SpDP, it was improved as compared with all other samples (71.53% surface coverage vs. 30.26%-43.87%; P less than .05).

“Based on these results, spray dried plasma was equivalent or superior to FFP in most of the in vitro hemostasis assays,” Dr. Meledeo said. “Reconstitution with glycine-HCl or glycine-HCl:glycine induced a superior von Willebrand function, but it was inferior in terms of supporting a flowing platelet adhesion to collagen.”

Dr. Bercovitz and Dr. Meledeo reported having no financial disclosures.

[email protected]

SOURCES: Bercovitz R et al. AABB 17 Abstract C20-A02B; Meledeo M et al. AABB 17 Abstract C21-A02B.