title: Batroxobin-induced clots exhibit delayed and reduced platelet contractile force in some patients with clotting factor deficiencies.
abstract: Thrombin causes platelet activation via multiple pathways, and deficient thrombin generation reduces platelet contractile force (PCF) during clot retraction. We hypothesized that PCF in blood samples from clotting factor-deficient patients would be diminished due to delayed or deficient thrombin generation. Blood samples from patients with fibrinogen, and factor V, VII, VIII, IX, X, XI and XIII deficiencies were compared to samples from normal controls. PCF in patient blood clotted with thrombin (1 NIH UmL(-1)) was compared to PCF in clots formed with batroxobin (0.25 micro g mL(-1)). PCF in the former should be normal, but PCF in the latter is dependent on thrombin generation within the sample and might be deficient. In factor VII-(n = 2, P < 0.05), factor VIII-(n = 6, P < 0.005) and factor XI-(n = 2, P < 0.05) deficient platelet-rich plasmas, PCF in batroxobin-induced clots was significantly lower than in thrombin-induced clots. In factor IX deficiency (n = 2), one patient had a dramatic reduction in PCF while a second patient had increased PCF. PCF was insignificantly (P = 0.346) reduced in two patients with factor X deficiency, and was normal in one patient with factor V deficiency. The factor X result is consistent with work in model systems, which indicates that as little as 1-3% factor X activity is sufficient to restore thrombin generation to normal. The factor V result probably indicates that the deficiency is incomplete. PCF in thrombin-induced clots was normal in all of these patients. Low fibrinogen and factor XIII deficiency reduced PCF in both thrombin- and batroxobin-induced clots. These results indicate that PCF is reduced, probably due to delayed thrombin generation, in some factor-deficient platelet-rich plasma samples.
authors.affiliation: Coagulation Special Studies Laboratory, Medical College of Virginia, VA, USA. mcarr@hsc.vcu.edu
authors.forename: M E
authors.initials: ME
authors.lastname: Carr
authors.forename: S L
authors.initials: SL
authors.lastname: Carr
authors.forename: T
authors.initials: T
authors.lastname: Tildon
authors.forename: L M C A
authors.initials: LM
authors.lastname: Fisher
authors.forename: E J
authors.initials: EJ
authors.lastname: Martin
mesh_terms: D012103:Batroxobin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology*; D016022:Case-Control Studies; D003018:Clot Retraction; D020147:Coagulation Protein Disorders / Q000097:blood* / Q000235:genetics; D004548:Elasticity; D006801:Humans; D066298:In Vitro Techniques; D015539:Platelet Activation / Q000187:drug effects; D013917:Thrombin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D012103:Batroxobin; D013917:Thrombin