Thrombotic microangiopathy and fibrinolysis after hump-nosed viper envenomation.
Vol. 57, No. 1, March 2012
Snake envenomation and resultant clinical
syndromes fascinate clinicians as they tend to have varied
presentations and we do not yet fully understand their
pathophysiology. We describe a patient who developed
thrombotic microangiopathy (TMA) and isolated
fibrinolysis following a hump-nosed viper (Hypnale sp.)
bite. Difference between the venom induced consumptive
coagulopathy (VICC) and the disseminated intravascular
coagulation (DIC) is discussed to understand the resultant
coagulopathy from this envenomation.
A 35-year old man who was bitten on his right leg by
Thrombotic microangiopathy and fibrinolysis after hump-nosed viper
H Karunatilake1, T Nayakarathna1, S Atapattu1, T Saparamadu1, S Dharmasena1
Ceylon Medical Journal 2012; 57: 45-46
a hump-nosed viper presented two hours after the bite.
Patient brought the dead snake to the hospital and it was
positively identified as a hump-nosed viper. Further species
classification was not done. On arrival at the hospital he
had local pain and there was mild oedema at the site of the
bite but no bleeding. He had no evidence of systemic
envenomation. His medical history was unremarkable. His
vital signs were stable and whole blood clotting time
(WBCT) was less than 20 minutes. His hemoglobin (Hb)
was 15 g/dL, platelets were 326,000/μl and serum creatinine
was 79.5 μmol/L. Prothrombin time (PT) and partial
thromboplastin time with kaolin (PTTK) were normal. He
was given intravenous normal saline to avoid dehydration.
After thirty-six hours urine output became low and his
creatinine rose to 671.8 μmol/L. Oliguric acute renal failure
1District General Hospital, Polonnaruwa, Sri Lanka.
Correspondence: HK, e-mail: <email@example.com>. Received 5 July and revised version accepted 29
September 2011. Competing interests: none declared.
Ceylon Medical Journal
was diagnosed and he was dialysed via a femoral
catheter. His Hb and platelet count started to drop and he
became icteric. His Hb was 7.3 g/dL and platelets dropped
to 15,000/μl. Unconjugated bilirubin was 102.6 μmol/L. His
WBCT, PT and PTTK remained within normal limits.
Lactate dehydrogenase was markedly elevated (9400 U/
L) and the D Dimer was greater than 2.4 mg/L. Blood
smear showed fragmented cells and schistocytes
confirming microangiopathic haemolysis. He underwent
two more cycles of dialysis. Then his family members
decided to seek alternative form of treatment and patient
left the hospital against medical advice.
Hump-nosed viper (genus Hypnale, family
Crotalinae) is a moderately venomous snake found in India
and Sri Lanka. In a series involving 10 hospitals in Sri
Lanka, hump-nosed viper bites accounted for 35% of
snake bite admissions . Most victims show local
swelling, pain and bleeding. Haemorrhagic blisters are seen
at the bite site and rarely have lead to amputations .
One series failed to report any systemic toxicity .
However, there are several reports of coagulopathy,
thrombocytopenia and acute renal failure occurring in
isolation and in combination after hump-nosed viper
envenomation [3-5]. In a series of 302 cases of confirmed
hump-nosed viper bites, 10% had developed acute renal
failure and 39% had incoagulable blood (20mins WBCT)
but data on platelet counts were not available .
The combination of acute renal failure,
thrombocytopenia and microangiopathic haemolytic
anaemia characterises thrombotic microangiopathy and
in snake envenoming it usually occurs in association with
VICC . In our patient coagulopathy was confined to a
raised D Dimer level suggesting hypofibrogenaemia. His
WBCT, PT and PTTK remained within normal limits.
Coagulopathy in snake envenomation depends on which
point the coagulation cascade is activated by the
procoagulant snake toxin. This is a major difference in
VICC from where coagulation is activated by tissue factor/
factor VII pathway . It is difficult to predict the type of
coagulopathy from the envenomation as most snake
venom contains a mixture of procoagulant toxins acting at
different points of the coagulation cascade. Apart from
basic clotting tests, few laboratory data are available on
the coagulopathy of snake venom in clinical studies. Out
of procoagulant toxins present in viper venom, Thrombin
Like Enzyme (TLE) mainly causes hypofibrogenaemia .
Often this hypofibrogenaemia is associated with
thrombocytopenia . Considering our patient’s elevated
D dimer (hypofibrogenaemia) and thrombocytopenia it is
safe to assume hump-nosed viper venom contains
predominantly TLEs as procoagulant toxin.
Unlike in DIC, coagulopathy in VICC has a rapid onset
and resolves within 24-48 hours. Despite the resolution of
the VICC, thrombotic microangiopathy progresses. This
suggests an involvement of a different toxin to
procoagulant toxin initiating TMA . In combination with
renal failure this clinical picture is similar to haemolytic-
uremic syndrome which usually results from a toxin causing
renal endothelial damage. It is possible that a toxin in
venom is causing a similar endothelial damage initiating
the thrombotic microangiopathy .
The treatment for hump-nosed envenomation is
supportive to date as there is no effective antivenom. Acute
renal failure is treated with dialysis and therapeutic
transfusions as required. TMA has been treated with
plasmapheresis. However, its role remains uncertain . It
is important to appreciate that the onset, progression and
resolution of VICC differ from that of DIC because it helps
to understand the clinical syndromes that result from snake
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