Hematotoxin producing snakes in Thailand

พญ.มชัฌิมา รอดเช้ือ พญ.อิสรีย ์หาญอุทยัรัศมี

Hematotoxin producing snakes

• Pit vipers (Crotalinae)

– Malayan pit viper (Calloselasma rhodostoma)

– Green pit viper (Trimeresurus spp.)

• Vipers (Viperinae)

– Russell’s viper (Daboia russelli siamensis)

Malayan’s pit viper

Green pit viper

Pathogenesis-Pit viper

• Thrombin-like effect

• Fibrinolytic effect

• Thrombocytopenia/platelet dysfunction

Thrombin effects

• Cleaving both fibrinopeptide A (FPA) and fibrinopeptide B (FPB) from fibrinogen

• Activating factor XIII

Snake venom thrombin-like enzymes (SVTLEs)

• Serine protease

• Stimulate fibrin formation

– Usually cleave fibrinopeptide A only

– Do not activate factor XIII

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

Fibrinolytic effect

• Fibrin deposition

• Tissue-type plasminogen activator

• GPV-Plasminogen activator

GPV-plasminogen

activator

Thrombocytopenia/ platelet dysfunction

• Direct venom effect

• C-type lectins

– Alboaggregin A, Alboaggregin B10

• Prevent platelet aggregation

– Inhibition of surface glycoprotein receptors

Russell’s viper

Pathogenesis-Viper

• Thromboplastin-like activity

• Hemolysis: Phospholipase A2

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)

Laboratory investigation

PT

APTT

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

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)

Results

109 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

12 individuals were excluded

• Unknown snake (7), cirrhosis (2), current warfarin intake (2), inadequate specimen (1)

97 patients

• 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)

• 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

• 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

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

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

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

Discussion

• Conventional VCT

– Low sensitivity for hypofibrinogenaemia (VCT>30 min)

• Depend on

– Fibrinogen quantity

– FDP levels from fibrinolysis

– Operator dependent

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

Thank you