Platelet factor V New York: A defect in factor V distinct from that in factor V Quebec resulting in impaired prothrombinase generation

Abstract

Studies were performed on a patient with a longstanding bleeding disorder whose major defects were impaired platelet prothrombinase activity in the absence of added factor Va, and a platelet factor V value that was either decreased or at the lower limit of normal when assayed on multiple occasions. In contrast, plasma factor V values were consistently normal. Unlike Scott Syndrome, in which platelet prothrombinase activity is decreased in both the presence and absence of added factor V, her platelets appeared to utilize added factor Va normally in supporting the generation of prothrombinase activity. These findings suggest an intrinsic defect in platelet factor V as the basis of her platelet prothrombinase defect. This defect appears to be different than that described in the Quebec platelet disorder (factor V Quebec). Immunoblot analyses of washed platelet lysates demonstrated a pattern of variably sized factor V molecules that was entirely similar to that observed in normal platelets, and both the heavy and light chains of her factor V after thrombin cleavage were of the same size as that observed in normal platelets. In addition, her platelet multimerin was normal and immunoblot analysis excluded the type of generalized granular protein defect and pathological proteolysis that has been suggested to explain the factor V defect in the Quebec platelet disorder. The findings in this patient thus suggest a new type of platelet factor V defect as the basis for the impaired capacity of her activated platelets to support prothrombinase generation. The findings further support an important role for platelet factor V in hemostasis.

Residual platelet factor V ensures thrombin generation in patients with severe congenital factor V deficiency and mild bleeding symptoms

“…Moreover, in a patient with a circulating FV inhibitor and undetectable plasma FV, platelet FV proved sufficient to ensure adequate hemostasis even during surgery. 39 The pivotal role of platelet FV is further supported by the bleeding diathesis associated with FV New York, 49 a selective deficiency of platelet FV with normal levels of plasma FV.…”

Quebec platelet disorder: features, pathogenesis and treatment

“…2) that is not evident in other platelet storage pool disorders [2,3,6,68,69]. As a result, western blot assays for degraded a-granule proteins can be used for the diagnostic evaluation of QPD [2-6] ( Fig.…”

Protease-Activated Receptor (PAR) 1 and PAR4 Differentially Regulate Factor V Expression from Human Platelets

“…In addition to the provision of phosphatidyl-serine (PS)-rich membranes for the assembly of coagulation complexes, platelets possess a unique, APCresistant, preactivated form of factor V (FV) (Alberio et al, 2000;Duckers et al, 2010), which is concentrated in a-granules from plasma sources. Platelet-FV represents 20% of the total amount of FV circulating in whole blood, and FV concentrations in the platelet exceed that of the plasma by 100-fold (Weiss et al, 2001). The importance of platelet-FV has been shown in clinical cases of bleeding associated with defects in FV storage or release (Tracy et al, 1984;Nesheim et al, 1986;Grigg et al, 1989;Weiss and Lages, 1997;Weiss et al, 2001;Diamandis et al, 2008).…”

“…Platelet-FV represents 20% of the total amount of FV circulating in whole blood, and FV concentrations in the platelet exceed that of the plasma by 100-fold (Weiss et al, 2001). The importance of platelet-FV has been shown in clinical cases of bleeding associated with defects in FV storage or release (Tracy et al, 1984;Nesheim et al, 1986;Grigg et al, 1989;Weiss and Lages, 1997;Weiss et al, 2001;Diamandis et al, 2008). More recently, patients with severe congenital FV deficiency were shown to be protected against a loss of thrombin generation and severe bleeding by residual FV concentrated in their platelet granules (Duckers et al, 2010).…”