Viper bites cause consumptive coagulopathy resulting in hypofibrinogenaemia. Whole-blood clotting time is a standard test used to assess bleeding risk. Prothrombin time (PT) and activated partial thromboplastin time (APTT) are better standardised assays that are widely available, but their diagnostic accuracy in viper bites remains unknown. Adult patients presumed bitten by green pit vipers (Cryptelytops sp.) were enrolled. Conventional venous clotting time (VCT), 20min whole-blood clotting time (20WBCT), PT with international normalized ratio (INR) and APTT were determined. A fibrinogen level below 1.0g/litre was used as the gold standard. There were 97 patients. The average age was 46.1 years and 49.5% were men. VCT >30min, INR >1.2 and fibrinogen level <1.0g/litre were found in 9.3, 10.3 and 7.2%, respectively. The sensitivities of VCT >30min, 20WBCT (N=55), INR and APTT were 57.0%, 85.7%, 85.7% and 57.1%, respectively. The respective specificities were 94.4%, 95.8%, 95.6% and 72.4%. Three hypofibrinogenaemic patients who did not receive antivenom because of VCT <30min had persistently normal VCT and went home without clinical bleeding. In conclusion, PT with INR can be an alternative test for evaluation of coagulopathy in green pit viper bitten patients with potentially improved inter-laboratory standardisation.

SummaryPlatelet aggregation and fibrinogen binding were studied in 15 individuals before and 7 days after the oral administration of ticlopidine (250 mg b.i.d.). Ticlopidine significantly inhibited platelet aggregation induced by adenosine diphosphate (ADP), the endoperoxide analogue U46619, collagen or low concentrations of thrombin, but did not inhibit platelet aggregation induced by epinephrine or high concentrations of thrombin. Ticlopidine inhibited 125I-fibrinogen binding induced by ADP, U46619 or thrombin (1 U/ml). The ADP scavengers apyrase or CP/CPK, added in vitro to platelet suspensions obtained before ticlopidine, caused the same pattern of aggregation and 125I-fibrihogen binding inhibition as did ticlopidine. Ticlopidine did not inhibit further platelet aggregation and 125I-fibrinogen binding induced in the presence of ADP scavengers. After ticlopidine administration, thrombin or U46619, but not ADP, increased the binding rate of the anti-GPIIb/IIIa monoclonal antibody 7E3 to platelets. Ticlopidine inhibited clot retraction induced by reptilase plus ADP, but not that induced by thrombin or by reptilase plus epinephrine, and prevented the inhibitory effect of ADP, but not that of epinephrine, on the PGE1-induced increase in platelet cyclic AMP. The number of high- and low-affinity binding sites for 3H-ADP on formalin-fixed platelets and their K d were not modified by ticlopidine. These findings indicate that ticlopidine selectively inhibits platelet responses to ADP.

Green pit viper bite is a common public health problem in Southeast Asia. Although most patients experience only local swelling, some may suffer from severe systemic bleeding that can be delayed. Venom antigenaemia was measured by enzyme-linked immunosorbent assay and correlated with clinical findings in 42 patients. Initial venom antigenaemia was not predictive enough for clinical uses. A kinetic study (n = 27) showed highest levels at presentation and, then, progressive decline. The average half-life was 27.5 h during the first three days and over 50 h on days 5-7 after bite. Two small subsets (7.4% each) showed persistently detectable venom on day 14 and a subsequent rise in venom antigenaemia. They were associated with prolonged thrombocytopaenia and coagulopathy, respectively. These data demonstrated the long half-life of the venom, suggesting that waiting for spontaneous resolution of coagulopathy is not preferable. In addition, the delayed venom disappearance, not the initial values, was correlated with haemostatic disorders.

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Although natural anticoagulant deficiencies are the established causes of thrombosis, their roles in bleeding are not fully studied. The objective is to correlate haemostatic factors with haemorrhagic symptoms quantified by a standardized questionnaire. Adult subjects were recruited from Bangkok and nearby provinces as part of routine health surveys/checkups. The validated MCMDM-1VWD form was used to assess their bleeding symptoms. At the same time, von Willebrand factor (VWF) activity, free protein S levels and protein C activity were measured. There were 5196 individuals. The mean age was 44.3 years (range 15-99) and 41% were male subjects. The mean bleeding score was -0.28 and 95% of subjects had scores between -2 and +2. The scores were lower in female subjects than in male subjects (-0.35 vs. -0.16, P < 0.001). Bleeding scores correlated negatively with age, VWF and protein C activities (Spearman's ρ-0.258, -0.091 and -0.098, respectively, all P < 0.001), but did not significantly correlate with protein S levels. Using multivariate analysis, female gender, VWF below 100 IU dL(-1), protein C below 100 IU dL(-1) and protein S over 150 IU dL(-1) significantly related to high (≥3) bleeding scores (adjusted odds ratio 1.95, 1.83, 1.56 and 2.84, P = 0.001, 0.001, 0.039 and 0.017, respectively). These findings may suggest interacting roles of VWF and natural anticoagulants in modifying bleeding symptoms.

SummaryNormal human platelets aggregated by thrombin undergo the release reaction and are not readily deaggregated by the combination of inhibitors hirudin, prostaglandin E1 (PGE1) and chymotrypsin. Released adenosine diphosphate (ADP) plays an important role in the stabilization of thrombin-induced human platelet aggregates. Since ticlopidine inhibits the platelet responses to ADP, we studied thrombin-induced aggregation and deaggregation of 14C-serotonin-labeled platelets from 12 patients with cardiovascular disease before and 7 days after the oral administration of ticlopidine, 250 mg b.i.d. Before and after ticlopidine, platelets stimulated with 1 U/ml thrombin aggregated, released about 80–90% 14C-serotinin and did not deaggregate spontaneously within 5 min from stimulation. Before ticlopidine, hirudin (5× the activity of thrombin) and PGE1 (10 μmol/1) plus chymotrypsin (10 U/ml) or plasmin (0.06 U/ml), added at the peak of platelet aggregation, caused slight or no platelet deaggregation. After ticlopidine, the extent of platelet deaggregation caused by the same inhibitors was significantly greater than before ticlopidine. The addition of ADP (10 μmol/1) to platelet suspensions 5 s after thrombin did not prevent the deaggregation of ticlopidine-treated platelets. Thus, ticlopidine facilitates the deaggregation of thrombin-induced human platelet aggregates, most probably because it inhibits the effects of ADP on platelets.