Hematotoxin producing snakes in Thailand พญ.ม ชฌ มา รอดเช อ พญ.อ สร ย หาญอ ท ยร ศม

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1 Hematotoxin producing snakes in Thailand พญ.ม ชฌ มา รอดเช อ พญ.อ สร ย หาญอ ท ยร ศม

2 Hematotoxin producing snakes Pit vipers (Crotalinae) Malayan pit viper (Calloselasma rhodostoma) Green pit viper (Trimeresurus spp.) Vipers (Viperinae) Russell s viper (Daboia russelli siamensis)

3 Malayan s pit viper

4 Green pit viper

5 Pathogenesis-Pit viper Thrombin-like effect Fibrinolytic effect Thrombocytopenia/platelet dysfunction

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10 Thrombin effects Cleaving both fibrinopeptide A (FPA) and fibrinopeptide B (FPB) from fibrinogen Activating factor XIII

11 Snake venom thrombin-like enzymes (SVTLEs) Serine protease Stimulate fibrin formation Usually cleave fibrinopeptide A only Do not activate factor XIII

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13 Thrombin-like effects Ineffective fibrin polymers Easily to break down Failure of clot cross-linking Destruction by fibrinolytic system Effective removal of fibrinogen from plasma Defibrination, Defibrinogenation Fibrinogenolytic enzyme

14 Fibrinolytic effect Fibrin deposition Tissue-type plasminogen activator GPV-Plasminogen activator

15 GPVplasminogen activator

16 Direct venom effect C-type lectins Thrombocytopenia/ platelet dysfunction Alboaggregin A, Alboaggregin B10 Prevent platelet aggregation Inhibition of surface glycoprotein receptors

17 Russell s viper

18 Pathogenesis-Viper Thromboplastin-like activity Hemolysis: Phospholipase A2

19 Thromboplastin-like factors Russell s viper venom activates Factor V, Factor X (RVV-V, RVV-X) Stimulate common hemostatic pathway Classic disseminated intravascular coagulopathy (DIC)

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21 Laboratory investigation

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23 PT

24 APTT

25 Whole blood clotting time (WBCT) The whole blood clotting time (WBCT) is the most frequently carried out coagulation test as an indicator for venom-induce coagulopathy Cheap Simple Bed-side test

26 Whole blood clotting time (WBCT) This test was originally described by Lee and White in 1913 In 1999, the World Health Organization (WHO) recommended another version of the WBCT, known as the 20 minutes WBCT (20WBCT)

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31 Results 109 patients 12 individuals were excluded 97 patients Adult >15 years Bitten by presumed green pit viper within 72 hours ED or snakebite clinic, King Chulalongkorn Memorial Hospital OCT 2008-DEC 2010 Unknown snake (7), cirrhosis (2), current warfarin intake (2), inadequate specimen (1) Mean age 46.1 (15-82) years, 48 (49.5%) men 12 (12.4%) patients received antivenom VCT>30 min without bleeding (9), marked oedema (3)

32 Conventional VCT: highest correlation coefficient with fibrinogen level PT and INR: highest area under the ROC curve APTT: less able to distinguish hypofibrinogenaemic patient from others

33 Diagnostic accuracy of 20WBCT and INR was superior than VCT (>30 min), and APTT PT (INR): not sensitive when use fibrinogen cut off level of 1.7 g/l

34 Results 3 patients had fibrinogen level <1.0 g/l but <30 min VCT, no one receive antivenom Followed for 3 days with daily VCT Normal without clinical bleeding None reported late any late complication

35 Discussion PT prolongation (INR>1.2): related to severe hypofibrinogenaemia (fibrinogen level<1g/l) Causes of PT prolongation Low fibrinogen Hyperfibrinolysis releasing fibrin degradation products (FDPs)=> interfere with fibrin polymerization PT normal in mild hypofibrinogenaemia, low sensitivity for cut off fibrinogen of 1.7g/L

36 Discussion APTT low diagnostic accuracy Inter-laboratory variation of universal cut off level 20WBCT Confirmed accuracy in predicting severe hypofibrinogenemia in this study However, this study included fewer 20WBCT than PT and VCT

37 Discussion Conventional VCT Low sensitivity for hypofibrinogenaemia (VCT>30 min) Depend on Fibrinogen quantity FDP levels from fibrinolysis Operator dependent

38 Conclusion PT or 20WBCT can be used for evaluation of green pit viper bitten patient Depending on testing convenience and availability Prolongation of either test suggests severe hypofibrinogenaemia that requires antivenom therapy

39 Thank you