acquired factor viii deficiency is caused by the development of autoantibodies directed against circulating coagulation factor viii , which inhibits its function [ 1 , 2 ] .
it may be associated with pregnancy , the postpartum period , autoimmune conditions , drugs , lymphoproliferative disorders , or malignancies . in approximately half of the diagnosed cases ,
we report a rare case of subdual hemorrhage in a man , who acquired factor viii inhibitors and developed coagulopathy after consuming toxin of the cobra , naja naja .
a 49-year - old male was admitted with a 10-day history of subcutaneous hemorrhage of the right shoulder ( fig . 1 ) and left thigh .
the patient was being treated with losartan 50 mg / day for hypertension and metformin 500 mg twice a day for diabetes .
he had eaten 10 g of dried gall bladder of a cobra , naja naja in thailand one month ago .
laboratory test showed a prolonged activated partial thromboplastin time ( aptt ) exceeding 120 seconds ( normal range , 30 - 47 seconds ) , not corrected with plasma mixing test .
his prothrombin time was 10 seconds ( normal range , 10 - 13 seconds ) , the level of fdp was 11.71 ug / ml ( normal range , below 5 ug / ml ) , and d - dimer was 3.42 ug / ml ( normal range , below 1.3 ug / ml ) . his hemoglobin was 7.0 g / dl and platelet count was 32310/l .
the factor viii level was less than 1% , and his factor viii inhibitor antibody titer was 246 bethesda units / ml ( normal range , 0 - 0.7 bethesda units / ml ) .
lupus anticoagulant antibody , anti - nuclear antibody and anti - phospholipid antibody were negative .
he was diagnosed with acquired factor viii deficiency . magnetic resonance imaging ( mri ) of the thigh showed hematomas in the left vastus medialis muscle ( fig .
the patient was treated with an intravenous infusion of factor viii 3,000 u ( 50 u / kg ) every 8 hours .
one month after treatment , the patient 's symptoms improved , but his factor viii inhibitor antibody titer was still high ( 147 bethesda units / ml ) .
he had an aptt exceeding 120 seconds due to the presence of high titers of factor viii inhibitor ( 217 bethesda units / ml ) .
brain ct scan revealed a mixed subacute subdural hematoma in the left fronto - temporo - occipital areas ( fig .
3 ) and recombinant factor vii was infused at a dose of 360 kiu / day . despite treatment , the patient 's bleeding worsened .
two weeks later , multifocal subarachnoid hemorrhages and intracranial hemorrhages in both cerebral hemispheres were revealed .
it results from the development of inhibitors , that typically interfere with the coagulant properties of factor viii [ 1 , 2 , 7 ] .
the clinical picture is characterized by spontaneous and often sudden onset of severe hemorrhage in a patient with no bleeding history .
more than 80% of patients have hemorrhages into the skin , muscles or soft tissues , and mucous membranes .
however , the spontaneous disappearance of inhibitors is unpredictable and may occur over many years .
for a better prognosis , eradication of the inhibitor and maintenance of normal level of clotting factor viii are important .
the therapeutic strategy is to stop the hemorrhage and reduce the autoantibody levels . bypassing products currently available for bleeding control
are recombinant activated factor vii ( rfviia ) and plasma - derived activated prothrombin complex concentrate ( apcc ) . in patients with a high inhibitor titer and severe hemorrhages , the extracorporeal removal of the autoantibody by therapeutic plasmapheresis can be used before factor concentrate treatment .
there are two case reports in korea which were successfully treated with combination therapy that included therapeutic plasmapheresis .
once hemostasis is achieved , autoantibody eradication is the second major goal of acquired hemophilia therapy .
the inhibitor may also be eradicated with immunosuppressive agents , including corticosteroids and cytotoxic drugs , such as cyclophosphamide , azathioprine , 6-mercaptopurine , and vincristine .
we report the first case of acquired factor viii deficiency in a patient , who suffered from coagulopathy after consuming the dried gallbladder of a cobra .
coagulopathy is a significant cause of both morbidity and mortality in snakebite patients [ 13 , 14 ]
. a wide variety of venom components can act as procoagulants , activating the coagulation system in vivo , and causing the consumption of coagulation factors , resulting in clinical anticoagulation .
fibrinogen clotting and fibrinolytic snake venom toxins exert a direct effect on the actual thrombus - forming protein , fibrinogen , but in varying ways .
fibrinogen may be split into fibrin and then degradation products , or it may be only partially split , leaving an ineffective form of fibrinogen circulating , the end result being an increased bleeding tendency .
snake venom inhibits platelet activity too , thus reducing their effectiveness in hemostasis [ 13 , 14 ] .
another study reported there is transient presence of an inhibitor to factors viii , ix and xi in cases of tiger snake envenomation . in our case ,
cobra toxin was probably the cause of development of factor viii inhibitor , since the acquired factor viii deficiency developed right after consuming the cobra toxin , and we did not find any other possible cause of acquired factor viii deficiency in this patient . perhaps cobra toxin entered the blood stream through damaged oral mucosa , and acted as factor viii inhibitor . in order to make a clear connection between cobra toxin and acquired factor viii deficiency , further evaluation about the effects of snake venom on individual coagulation factors is needed .
 acquired factor viii deficiency is very rare , often fatal . 
 it is associated with pregnancy , autoimmune diseases , malignancy , and drugs , although no underlying cause is found in 50% . 
 a 49-year - old male was referred with right shoulder bruising . 
 the coagulation test showed a prolonged activated partial thromboplastin time . 
 the factor viii level was less than 1% , and the factor viii inhibitor antibody titer was 246 bethesda units / ml . the findings were compatible with acquired factor viii deficiency . 
 he had consumed the dried gallbladder of a cobra , naja naja , for two weeks , it contained venom . 
 after the initial treatment with factor viii , he did not take supplemental coagulation factor viii . 
 the patient was readmitted with left forearm swelling . 
 he lost consciousness suddenly and brain computed tomography ( ct ) revealed a subdural hematoma . despite administering recombinant factor vii , 
 his bleeding was not controlled and he died . 
INTRODUCTION
CASE REPORT
DISCUSSION