scholarly journals Effects of fresh-frozen plasma and its cryosupernatant fraction on von Willebrand factor multimeric forms in chronic relapsing thrombotic thrombocytopenic purpura

Blood ◽  
1985 ◽  
Vol 65 (5) ◽  
pp. 1232-1236 ◽  
Author(s):  
JL Moake ◽  
JJ Byrnes ◽  
JH Troll ◽  
CK Rudy ◽  
SL Hong ◽  
...  

Abstract Remission plasma samples of some patients with chronic relapsing thrombotic thrombocytopenic purpura (TTP) contain unusually large von Willebrand factor (vWF) multimers similar to those produced by normal human endothelial cells in culture. The infusion of the cryosupernatant fraction of normal plasma is as effective as normal fresh-frozen plasma (FFP) in the treatment or prevention of TTP episodes in patients with the chronic relapsing form of TTP. Three patients with chronic relapsing TTP during remission have unusually large vWF multimers present in their plasma. Two of the patients were transfused once with FFP, one of the two received cryosupernatant on three occasions, and the third patient was studied before and immediately after plasma exchange. Unusually large vWF multimers decreased or disappeared from patient plasma samples within 1/2 to 1 1/2 hours following the transfusion of FFP (on two occasions) or cryosupernatant (on two of three occasions), and immediately after plasma exchange (on one occasion). The patient who received cryosupernatant was studied serially after the infusions. Unusually large vWF multimers returned to her plasma within ten to 24 hours and persisted thereafter. Unusually large vWF multimers did not disappear from patient remission plasma samples, or from the culture medium removed from normal human endothelial cells, when these fluids were incubated in vitro with either normal FFP or cryosupernatant. We conclude that an activity in FFP, and its cryosupernatant fraction, promoted the rapid in vivo disappearance of unusually large vWF multimers from the plasma of two patients with chronic relapsing TTP in remission, and plasma exchange reversed the abnormality in a third patient who was in partial remission. Neither FFP nor cryosupernatant directly converted unusually large multimers to smaller vWF forms in vitro in the fluid phase. These results indicate that an activity in the cryosupernatant fraction of normal plasma is involved in vivo in controlling the metabolism of unusually large vWF multimers, and that this process is defective in some chronic relapsing TTP patients.

Blood ◽  
1985 ◽  
Vol 65 (5) ◽  
pp. 1232-1236 ◽  
Author(s):  
JL Moake ◽  
JJ Byrnes ◽  
JH Troll ◽  
CK Rudy ◽  
SL Hong ◽  
...  

Remission plasma samples of some patients with chronic relapsing thrombotic thrombocytopenic purpura (TTP) contain unusually large von Willebrand factor (vWF) multimers similar to those produced by normal human endothelial cells in culture. The infusion of the cryosupernatant fraction of normal plasma is as effective as normal fresh-frozen plasma (FFP) in the treatment or prevention of TTP episodes in patients with the chronic relapsing form of TTP. Three patients with chronic relapsing TTP during remission have unusually large vWF multimers present in their plasma. Two of the patients were transfused once with FFP, one of the two received cryosupernatant on three occasions, and the third patient was studied before and immediately after plasma exchange. Unusually large vWF multimers decreased or disappeared from patient plasma samples within 1/2 to 1 1/2 hours following the transfusion of FFP (on two occasions) or cryosupernatant (on two of three occasions), and immediately after plasma exchange (on one occasion). The patient who received cryosupernatant was studied serially after the infusions. Unusually large vWF multimers returned to her plasma within ten to 24 hours and persisted thereafter. Unusually large vWF multimers did not disappear from patient remission plasma samples, or from the culture medium removed from normal human endothelial cells, when these fluids were incubated in vitro with either normal FFP or cryosupernatant. We conclude that an activity in FFP, and its cryosupernatant fraction, promoted the rapid in vivo disappearance of unusually large vWF multimers from the plasma of two patients with chronic relapsing TTP in remission, and plasma exchange reversed the abnormality in a third patient who was in partial remission. Neither FFP nor cryosupernatant directly converted unusually large multimers to smaller vWF forms in vitro in the fluid phase. These results indicate that an activity in the cryosupernatant fraction of normal plasma is involved in vivo in controlling the metabolism of unusually large vWF multimers, and that this process is defective in some chronic relapsing TTP patients.


2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Allan M. Klompas ◽  
Noud van Helmond ◽  
Justin E. Juskewitch ◽  
Rajiv K. Pruthi ◽  
Matthew A. Sexton ◽  
...  

AbstractConvalescent plasma is used to treat COVID-19. There are theoretical concerns about the impact of pro-coagulant factors in convalescent plasma on the coagulation cascade particularly among patients with severe COVID-19. The aim of this study was to evaluate the coagulation profile of COVID-19 convalescent plasma. Clotting times and coagulation factor assays were compared between fresh frozen plasma, COVID-19 convalescent plasma, and pathogen-reduced COVID-19 convalescent plasma. Measurements included prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, D-dimer, von Willebrand factor activity, von Willebrand factor antigen, coagulation factors II, V, VII–XII, protein S activity, protein C antigen, and alpha-2 plasmin inhibitor. Clotting times and coagulation factor assays were not different between COVID-19 convalescent plasma and fresh frozen plasma, except for protein C antigen. When compared to fresh frozen plasma and regular convalescent plasma, pathogen reduction treatment increased activated partial thromboplastin time and thrombin time, while reducing fibrinogen, coagulation factor II, V, VIII, IX, X, XI, XII, protein S activity, and alpha-2 plasmin inhibitor. The coagulation profiles of human COVID-19 convalescent plasma and standard fresh frozen plasma are not different. Pathogen reduced COVID-19 convalescent plasma is associated with reduction of coagulation factors and a slight prolongation of coagulation times, as anticipated. A key limitation of the study is that the COVID-19 disease course of the convalesced donors was not characterized.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1464-1464 ◽  
Author(s):  
Amanda Bruder Rassi ◽  
Tania RFR Rocha ◽  
Alberto Q Farias ◽  
Livia Caroline Barbosa Mariano ◽  
Elbio Antonio D'Amico

Abstract Introduction: In vitro studies have shown that transfusion of fresh frozen plasma (FFP) has limited efficacy in correcting coagulopathy in cirrhosis. This study aims to assess the effect of FFP transfusion on endogenous thrombin potential (ETP) in patients with cirrhosis with abnormal coagulation test results. Methods: Using a stringent protocol for control of pre-analytic variables, blood samples were collected before and up to 8 hours after FFP transfusion. All samples were tested for INR, aPTT and ETP. The ETP assay was performed in platelet-poor plasma, using an automated fluorometer (CAT, Netherlands), using the technique developed by Hemker and modified by Tripodi. ETP was defined as the area under ROC curve and results were expressed as the ratio of ETP with thrombomodulin addition to ETP without (used to mimic in vivo conditions when patients are transfused). Results: 42 patients were included (male n=28; Child-B n= 11; Child-C n=31). Patients underwent FFP transfusion prior to high-risk invasive procedures (n=25), for treatment of bleeding (n=10) or for both reasons (n=6). The mean dose of FFP was 11.3 ml/kg (95% CI 9.16 - 20.46). After transfusion, INR decreased from 2.6±1,4 to 2.09±0.5 (p<0.0001) and aPTT from 1.47±0.5 to 1.27±0.26 (p<0.0001). At baseline, normal or above normal values of ETP ratio (³0.66) were found in 37 (88%) patients, and mean values remained largely unchanged after FFP transfusion (0.75±0.22; median 0.82 before to 0.76±0.16; median 0.81 after transfusion; p=0.56). The results for INR, aPTT and ETP are shown in figure 1. During the one-week follow-up period, 4 patients (9,5%) had acute reactions to transfusion, including fluid overload and allergic reactions. Of the 31 patients that underwent invasive procedures, four had severe bleeding. Discussion: FFP transfusion at standard doses ameliorated INR and aPTT, but did not increase thrombin generation corrected by thrombomodulin. That might be explained by the fact the former tests detect only 5% of the amount of thrombin generated. Besides, they are performed without the addition of thrombomodulin, an endothelial protein with anticoagulant effects, to which patients with cirrhosis have shown to be resistant. Patients were exposed to the risks of transfusions, without a clear benefit in the improvement in thrombin generation and decreasing the risk of bleeding. Our results call into question the common use of INR and aPTT for guiding the transfusion policy of FFP when treating coagulopathy in cirrhosis. Figure 1: Results showing comparison before and after FFP transfusion for (A) INR, (B) aPTT and (C) ETP ratio with and without thrombomodulin. Disclosures No relevant conflicts of interest to declare.


1987 ◽  
Author(s):  
A Derlon ◽  
A Le Querrec ◽  
E Lebrun ◽  
G Tobelem ◽  
M Thomas

As we previously described, plasma infusion increased platelet count (PC) in four patients with IIB von Willebrand disease with severe thrombocytopenia. In a sixty years old patient in the same family, with chronic thrombocytopenia (PC = 30 000/ml) associated to an absence of large von Willebrand Factor multi-mers (vWF) in plasma, we successfully treated :1° A gastrointestinal bleeding episode with fresh frozen plasma infusion (15ml/Kg/day).2° Three months later a severe epistaxis with cryoprecipi-tate supernatant (15ml/Kg/day).During these bleeding episodes, the efficiency of these two treatments on the PC could be ascertained according to the following figureWe observed after ten days of these two treatments the following biological effects : a normalisation of vWF cross immunoelectrophoresis, of ristocetin induced normal platelet aggregation by patient's plasma, and of patient's plasma vWF binding to control platelets.In conclusion a factor appears to be present in both fresh frozen plasma and cryoprecipitate supernatant which prevents the abnormal binding of von Willebrand Factor (in this IIB von Willebrand disease) to the patient's platelets.


1992 ◽  
Vol 68 (06) ◽  
pp. 687-693 ◽  
Author(s):  
P T Larsson ◽  
N H Wallén ◽  
A Martinsson ◽  
N Egberg ◽  
P Hjemdahl

SummaryThe significance of platelet β-adrenoceptors for platelet responses to adrenergic stimuli in vivo and in vitro was studied in healthy volunteers. Low dose infusion of the β-adrenoceptor agonist isoprenaline decreased platelet aggregability in vivo as measured by ex vivo filtragometry. Infusion of adrenaline, a mixed α- and β-adrenoceptor agonist, increased platelet aggregability in vivo markedly, as measured by ex vivo filtragometry and plasma β-thromboglobulin levels. Adrenaline levels were 3–4 nM in venous plasma during infusion. Both adrenaline and high dose isoprenaline elevated plasma von Willebrand factor antigen levels β-Blockade by propranolol did not alter our measures of platelet aggregability at rest or during adrenaline infusions, but inhibited adrenaline-induced increases in vWf:ag. In a model using filtragometry to assess platelet aggregability in whole blood in vitro, propranolol enhanced the proaggregatory actions of 5 nM, but not of 10 nM adrenaline. The present data suggest that β-adrenoceptor stimulation can inhibit platelet function in vivo but that effects of adrenaline at high physiological concentrations are dominated by an α-adrenoceptor mediated proaggregatory action.


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