HIV-associated Thrombotic Thrombocytopenic Purpura — What We Know So Far

2012 ◽  
Vol 08 (02) ◽  
pp. 89 ◽  
Author(s):  
Muriel Meiring ◽  
Mike Webb ◽  
Dominique Goedhals ◽  
Vernon Louw ◽  
◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Von Willebrand Factor ◽  
Thrombus Formation ◽  
Thrombocytopenic Purpura ◽  
Immunodeficiency Virus ◽  
Platelet Deposition ◽  
Initial Onset ◽  
Life Threatening ◽  
Von Willebrand ◽  
Willebrand Factor

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease characterised by microvascular platelet deposition and thrombus formation in selected organs, resulting in microangiopathic haemolytic anaemia, thrombocytopenia, neurological symptoms and renal failure. Typically a very rare disorder, TTP is being seen with increased frequency in patients infected with the human immunodeficiency virus (HIV). Deficiency of the von Willebrand factor cleavage protease, ADAMTS13, has been implicated as the cause of TTP. However, the pathophysiology of HIV-associated TTP and the thrombotic potential in these patients are not known. This article provides not only an overview of the literature regarding HIV-associated TTP, but also presents new data on this disease. We propose a mechanism for the initial onset of HIV-associated TTP that includes the release of extreme amounts of von Willebrand factor and the downregulation of ADAMTS13 and/or the production of autoantibodies to ADAMTS13.

COAGULATION STUDIES IN THROMBOTIC THROMBOCYTOPENIC PURPURA, WITH SPECIAL REFERENCE TO VON WILLEBRAND FACTOR ABNORMALITIES

1987 ◽  
Author(s):  
Hoyu Takahashi ◽  
Wataru Tatewaki ◽  
Tadao Nakamura ◽  
Masaharu Hanano ◽  
Ken Wada ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Von Willebrand Factor ◽  
Thrombus Formation ◽  
Tissue Type ◽  
Thrombocytopenic Purpura ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Plasmin Inhibitor

The profile of blood coagulation and fibrinolysis was studied in detail in 8 patients with thrombotic thrombocytopenic purpura (TTP), who had most of the characteristic findings such as fluctuating neurologic signs, schistocytic hemolytic anemia, marked thrombocytopenia, renal abnormalities and fever. Fibrinogen (2.2-3.6 g/L) and factor XIII levels were normal in all patients, while FDP values were slightly elevated (from below 5 to 4-0 mg/L). Anti thrombin III, alpha 2-plasmin inhibitor and plasminogen were normal in all patients except one with elevated FDP. Alpha 2-macroglobulin was normal as well. Plasmin-alpha 2-plasmin inhibitor complex measured by an enzyme-immunoassay was either normal or marginally elevated. Tissue-type plasminogen activator antigen was elevated to 5.2-14.5 μg/L. Protein C activity and antigen were either normal or elevated, while protein S antigen was decreased in 3 patients. Factor VIII activity and von Willebrand factor antigen (vWf:Ag) and ristocetin cofactor (RCcf) were either normal or elevated, but RCof/vWf:Ag ratio was decreased (mean 0.546 ± SD 0.1876). Crossed immunoelectrophoresis and SDS-agarose gel electrophoresis revealed that the hemostatically most active, high-molecular-weight vWf multimers were absent from or relatively decreased in TTP plasma. In addition, a vWf fragment with a faster mobility than the major vWf was demonstrated in some patients. Histidine-rich glycoprotein and fibronectin were decreased in 3 and 4 patients, respectively. Most of these abnormal findings were nearly normalized in remission. Although the pathogenesis of TTP is still uncertain, these results indicate that in contrast to disseminated intravascular coagulation, the intravascular generation of thrombin and plasmin was minimal in TTP, and suggest that the high-molecular-weight multimer vWf and fibronectin are consumed probably due to their participation in platelet thrombus formation in addition to platelet aggregating factor.

scholarly journals Cost effectiveness of caplacizumab in acquired thrombotic thrombocytopenic purpura

Blood ◽  
2020 ◽  
Author(s):  
George Goshua ◽  
Pranay Sinha ◽  
Jeanne Elise Hendrickson ◽  
Christopher A Tormey ◽  
Pavan Bendapudi ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Von Willebrand Factor ◽  
Organ Damage ◽  
Hospital Length Of Stay ◽  
Sensitivity Analyses ◽  
Thrombocytopenic Purpura ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Relapse Rates

Acquired thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease characterized by thrombotic microangiopathy leading to end-organ damage. The standard of care (SOC) treatment is therapeutic plasma exchange (TPE) alongside immunomodulation with steroids, with increasing use of rituximab +/- other immunomodulatory agents. The addition of caplacizumab, a nanobody targeting von Willebrand factor, was shown to accelerate platelet count recovery and reduce TPE treatments and hospital length of stay in TTP patients treated in the TITAN and HERCULES trials. The addition of caplacizumab to SOC also led to increased bleeding due to transient reductions in von Willebrand factor and increased relapse rates. Using data from TITAN and HERCULES on caplacizumab, we performed the first-ever cost effectiveness analysis in TTP. Over a 5-year period, the projected incremental cost effectiveness ratio (ICER) in our Markov model was $1,482,260, significantly above the accepted 2019 US willingness-to-pay of $195,300. One-way sensitivity analyses showed the utility of the well state and the cost of caplacizumab to have the largest effects on ICER, with a reduction in caplacizumab cost demonstrating the greatest impact on lowering the ICER. In a probabilistic sensitivity analysis, SOC was favored over caplacizumab in 100% of 10,000 iterations. Our data indicate that the addition of caplacizumab to SOC in treatment of acquired TTP is not cost effective due to the high cost of the medication and its failure to improve relapse rates. The potential impact of caplacizumab on health system cost using longer-term follow-up data merits further study.

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