TYPE IIB VON WILLEBRAND DISEASE WITH CHRONIC THROMBOCYTOPENIA : BENEFICIAL EFFECT OF CRYOPRECIPITATE SUPERNATANT INFUSION ON PLATELET COUNT AND BLEEDING

1987 ◽  
Author(s):  
A Derlon ◽  
A Le Querrec ◽  
E Lebrun ◽  
G Tobelem ◽  
M Thomas
Keyword(s):  
Platelet Count ◽  
Von Willebrand Factor ◽  
Fresh Frozen Plasma ◽  
Von Willebrand Disease ◽  
Severe Thrombocytopenia ◽  
Plasma Infusion ◽  
Fresh Frozen ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Frozen Plasma

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.

scholarly journals Clinical guidelines for cryoprecipitate transfusions

2020 ◽  
Vol 65 (1) ◽  
pp. 87-114
Author(s):  
G. M. Galstyan ◽  
T. V. Gaponova ◽  
E. B. Zhiburt ◽  
E. N. Balashova ◽  
A. L. Berkovskiy ◽  
...  
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
Factor Xiii ◽  
Fresh Frozen Plasma ◽  
Von Willebrand Disease ◽  
Fresh Frozen ◽  
Congenital Afibrinogenemia ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Disease Factor

Background. Cryoprecipitate is made from fresh-frozen plasma (FFP) and contains fibrinogen, factor VIII, factor XIII, von Willebrand factor, fibronectin and fibrinogen.Aim. To provide information on the composition and methods of production, storage, transportation and clinical use of cryoprecipitate.General findings. Cyoprecipitate is manufactured by slowly thawing FFP at 1–6°C. This precipitates out cryoproteins: factor VIII, von Willebrand factor, factor XIII, fibronectin and fibrinogen. After centrifugation, the cryoproteins are resuspended in a reduced volume of plasma. Cryoprecipitate is stored at temperatures not exceeding –25° С for 36 months. Indications for cryoprecipitate transfusion are hemophilia A, von Willebrand disease, factor XIII deficiency, congenital afibrinogenemia and hypofibrinogenemia, acquired hypofibrinogenemia. These indications can occur in obstetrics, neonatology, cardiac surgery, neurosurgery, hematology, orthopaedics, and general surgery during liver transplantation and disseminated intravascular coagulation.

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 ◽  
...  
Keyword(s):  
Plasma Exchange ◽  
Fresh Frozen Plasma ◽  
Plasma Samples ◽  
Fresh Frozen ◽  
Normal Human ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Frozen Plasma

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.

scholarly journals VOLUME PLASMA DAN FAKTOR VIII DALAM KRIOPRESIPITAT

2016 ◽  
Vol 19 (1) ◽  
pp. 9
Author(s):  
Dian Widyaningrum ◽  
Purwanto AP ◽  
Julia Setyati
Keyword(s):  
Factor Viii ◽  
Blood Group ◽  
Von Willebrand Factor ◽  
Plasma Volume ◽  
Fresh Frozen Plasma ◽  
Factor Viii Level ◽  
Viii Level ◽  
Fresh Frozen ◽  
Von Willebrand ◽  
Willebrand Factor

Blood product such as cryoprecipitate required a quality control. This includes development, implementation and the standard operating procedures use of each step of the process in the production of cryoprecipitated substance to ensure that the produced product contains a minimum of 80 international units (IU) of factor VIII. Cryoprecipitation is prepared from fresh frozen plasma that thawed and centrifuge by immediate spinning the excess plasma which then removed and leaving approximately 40ml which deposit 10 mL cryoprecipitate. One unit of cryoprecipitate contain 70–80 IU/unit factor VIII, ≥100 mg/unit von Willebrand factor, fibrinogen 5–10 mg/dL. The levels of factor VIII and von Willebrand factor (VWF) lowered in individuals with blood group O compared to individuals groups with non-O blood. This research is aimed to investigate whether plasma volume are correlated with the levels of factor VIII in cryoprecipitation. In this study purposive sampling is done in which 25 bags of cryoprecipitate materials (was storage for 11 months) from all types of blood group which were taken from storage, thawed, weighed and the plasma volume measured. Factor VIII was measured by coagulometric method. The researcher used Spearman correlation test to analyze the product, with significance degree p<0.05 and confidence interval 95%. In this study it is found plasma volume which was not related to the factor VIII level in cryoprecipitattion substance (p=0.585). Mean plasma volume of the cryoprecipitated matter was 56 mL, mean factor VIII was 83.3UI. Highest factor VIII level was 160.6 UI of cryoprecipitated blood group AB and lowest factor VIII level was 21.3 UI of cryoprecipitated blood group A.

Studies with the Nanobody That Detects the Gain-of-Function of von Willebrand Factor in a Cohort of Patients with Type 2B von Willebrand Disease: Correlation with Platelet Count, VWF Multimers and Molecular Defects.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1011-1011 ◽  
Author(s):  
Augusto B. Federici ◽  
Luciano Baronciani ◽  
Maria T. Canciani ◽  
Barbara Moroni ◽  
Carlo Balduini ◽  
...  
Keyword(s):  
Platelet Count ◽  
Von Willebrand Factor ◽  
Antibody Fragment ◽  
Von Willebrand Disease ◽  
Stress Conditions ◽  
Giant Platelets ◽  
Additional Tool ◽  
A1 Domain ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Background: Type 2B von Willebrand disease (VWD) is an inherited bleeding disorder caused by abnormal von Willebrand factor (VWF) that displays increased affinity to the platelet glicoprotein 1b alpha (GpIba) and is due to a group of mutations clustered within VWF A1 domain. Such an enhanced 2BVWF-GpIba binding usually result in loss of large VWF multimers and moderate-mild thrombocytopenia. A llama-derived antibody fragment (AuVWFa11) recognizing the GpIba-binding conformation has been recently developed (Blood2005;106:3035). Aims and design of the study: to further explore the usefulness of AuVWFa11 in type 2B diagnosis, we have prospectively tested AuVWFa11 in our cohort of 16 patients previously characterized by platelet count, VWF multimers and mutations. Methods: Data of platelet count with mean platelet volume (MPV) and morphologic evaluation of the blood smear to search for giant platelets or aggregates were associated with the history of physiologic or pathologic stress conditions such as pregnancy, infections, surgery or use of DDAVP. All patients were diagnosed by ristocetin induced platelet agglutination (RIPA) in the Platelet Rich Plasma (PRP), ristocetin cofactor activity (VWF:RCo) with VWF antigen (VWF:Ag), multimeric structure of VWF. Mutations within VWF A1 domain were searched for and confirmed by sequencing exon 28. AuVWFa11 was tested in 40 normal individuals (expressed as % of active VWF in normal pool plasma =0.70±0.13) and in type 2B. Results: Data (mean ± SD) of the AuVWFa11 tested in the 16 patients with type 2B VWD are correlated with the main phenotypic data and genotype (Table1). Platelet count &lt; 140,000 was found at baseline in only 3/16 (%), but was observed after stress conditions in 12/16 cases (%); no reduced platelet counts was found in 4/16 patients (%) from two different families (R1308L, R1341Q). An increased MPV was found in 12 cases but giant platelet and aggregates in only 1 case. Activated VWF as tested by AuVWFa11 was positive in all but 3 (R1308L) cases, with values ranging from 2 to 6 times higher than normal controls: values &gt; 3 correlate with loss of large VWF multimers and mild-moderate thrombocytopenia. Conclusions: The AVWF11a can show activated VWF in most type 2B VWD patients, especially when 2B VWF mutants induce significant loss of large multimers and thrombocytopenia. Therefore AuVWF11a can be a useful additional tool in the diagnosis of type 2B VWD. Table 1 Mutation (n) RIPA (mg/ml) VWF.Ag (U/dL) Plat Count (×10^9/L) MPV (micron^3) Loss of HMW Mult AuVWFa11 (ratioNPP) R1306W (5) 0.65 40±9 165±39 10.3±2.3 YES 3.7±1.5 R1308C (3) 0.72 53±16 163±61 11.5±1.9 YES 3.3±2.3 R1308L (3) 0.50 48±13 341±104 8.1±3.1 NO 0.5±0.2 I1309V (1) 0.40 115 222 11.8 PARTIAL 2.1 V1316M (2) 0.50 32±7 119±30 9.2±2.4 YES 4.4±0.1 P1337L (1) 0.50 48 222 9.5 PARTIAL 1.3 R1341Q (1) 0.67 43 422 9.9 PARTIAL 2.9

Clinical and molecular predictors of thrombocytopenia and risk of bleeding in patients with von Willebrand disease type 2B: a cohort study of 67 patients

Blood ◽  
2009 ◽  
Vol 113 (3) ◽  
pp. 526-534 ◽  
Author(s):  
Augusto B. Federici ◽  
Pier M. Mannucci ◽  
Giancarlo Castaman ◽  
Luciano Baronciani ◽  
Paolo Bucciarelli ◽  
...  
Keyword(s):  
Platelet Count ◽  
Confidence Interval ◽  
Von Willebrand Disease ◽  
Stress Conditions ◽  
Severe Thrombocytopenia ◽  
Risk Of Bleeding ◽  
Platelet Receptor ◽  
Low Platelet Count ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Type 2B von Willebrand disease (VWD2B) is caused by an abnormal von Willebrand factor (VWF) with increased affinity for the platelet receptor glycoprotein Ib-α (GPIb-α) that may result in moderate to severe thrombocytopenia. We evaluated the prevalence and clinical and molecular predictors of thrombocytopenia in a cohort of 67 VWD2B patients from 38 unrelated families characterized by VWF mutations. Platelet count, mean platelet volume, and morphologic evaluations of blood smear were obtained at baseline and during physiologic (pregnancy) or pathologic (infections, surgeries) stress conditions. Thrombocytopenia was found in 20 patients (30%) at baseline and in 38 (57%) after stress conditions, whereas platelet counts were always normal in 16 patients (24%) from 5 families carrying the P1266L/Q or R1308L mutations. VWF in its GPIb-α–binding conformation (VWF–GPIb-α/BC) was higher than normal in all except the 16 cases without thrombocytopenia (values up to 6-fold higher than controls). The risk of bleeding was higher in patients with thrombocytopenia (adjusted hazard ratio = 4.57; 95% confidence interval, 1.17-17.90) and in those with the highest tertile of bleeding severity score (5.66; 95% confidence interval, 1.03-31.07). Prediction of possible thrombocytopenia in VWD2B by measuring VWF–GPIb-α/BC is important because a low platelet count is an independent risk factor for bleeding.

scholarly journals Acquired Deficiency of von Willebrand Factor-Cleaving Protease in a Patient With Thrombotic Thrombocytopenic Purpura

Blood ◽  
1998 ◽  
Vol 91 (8) ◽  
pp. 2839-2846 ◽  
Author(s):  
Miha Furlan ◽  
Rodolfo Robles ◽  
Max Solenthaler ◽  
Bernhard Lämmle
Keyword(s):  
Platelet Count ◽  
Plasma Exchange ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Von Willebrand Factor ◽  
Protease Activity ◽  
Temporary Increase ◽  
Severe Thrombocytopenia ◽  
Thrombocytopenic Purpura ◽  
Von Willebrand ◽  
Willebrand Factor

Plasma of patients with thrombotic thrombocytopenic purpura (TTP) has been shown to contain unusually large von Willebrand factor (vWF) multimers that may cause platelet agglutination in vivo. Fresh frozen plasma infusions and plasma exchange represent the most efficient therapy of acute TTP. A specific protease responsible for cleavage of vWF multimers has been recently isolated from normal human plasma and was found to be deficient in four patients with chronic relapsing TTP. We examined the activity of the vWF-cleaving protease in plasma samples collected over a period of 400 days from a further patient with recurrent episodes of TTP who was treated by plasma exchange, plasma infusion, vincristine, corticosteroid therapy, and splenectomy. Complete deficiency of the vWF-cleaving protease was established during the first episode of TTP. The ensuing normalization of the platelet count was associated with the appearance of the protease activity. Three months after remission from the initial TTP event, the vWF-cleaving protease again disappeared and the platelet count gradually decreased. Relapses of severe thrombocytopenia occurred 7 and 11 months after the first acute episode of TTP. Deficient protease activity was associated with the presence in the patient plasma of an inhibitor that was found to be an IgG. Plasma exchange/infusion was followed by a temporary increase in the antibody titer, whereas treatment with vincristine led to a recovery of the platelet count without affecting the inhibitor concentration. Splenectomy and corticosteroid treatment resulted in disappearance of the autoantibody and normalization of the protease activity and of the platelet count. Our data suggest that the thrombocytopenia in this patient with TTP was associated with a lack of the vWF-cleaving protease activity depleted by an autoimmune mechanism. This case, together with our previously reported patients, leads us to conclude that acquired as well as constitutional deficiency of the vWF-cleaving protease may predispose to TTP.

Sign in / Sign up

Export Citation Format

Share Document