Author
Information
Neha Saxena*, A. R.
Chauhan**
(* Third
Year Resident, ** Additional Professor. Department of Obstetrics and
Gynecology, Seth GS Medical College and KEM
Hospital , Mumbai , India
Abstract
Warfarin
is a coumarin anticoagulant widely used for prophylactic as well as therapeutic
anti-coagulation.[1] Despite being a life-saving drug, special
attention and careful monitoring are required during administration because of potential
adverse effects.[2] Of the many complications and adverse effects,
intraperitoneal bleeding is exceptional and may occur either spontaneously
without any evident cause, or with trivial trauma. We report a case of
spontaneous intraperitoneal hemorrhage secondary to warfarin toxicity,
mimicking signs and symptoms of ruptured ectopic pregnancy.
Introduction
Warfarin
is a life-saving drug that is extensively used as an anticoagulant in the
prophylaxis of various serious conditions like deep venous thrombosis,
pulmonary thromboembolism, valvular heart disease, atrial fibrillation,
recurrent systemic embolization, recurrent myocardial infarction, prosthetic
heart valves and prosthetic implants. However, serious adverse effects are
encountered if coagulation profile is not monitored cautiously during its
administration; these may range from easy bruising of tissues with minimal or
no trauma, to serious life threatening conditions like intracranial bleed or
massive intraperitoneal bleeding. Other adverse effects are ecchymosis,
purpura, epistaxis, hematemesis, melena, and soft tissue hematomas. The most
common complication of warfarin administration is intraabdominal bleeding
(intraperitoneal, extraperitoneal, retroperitoneal).[2, 3]
Case Report
A 34 year
old para 2 living 2, case of ulcerative colitis and deep venous thrombosis
(DVT) since last 5 years, on daily treatment with tablet azathioprine 100 mg
and tablet warfarin 5 mg, presented to us with a complaint of sudden onset pain
in lower abdomen for 5 days; there were no aggravating or relieving
factors. She had undergone tubal
ligation following her last delivery and had no menstrual complaints, bleeding
or discharge per vaginum. There were no bladder complaints; however, she gave a
history of passage of blood in stools since last 5 years. There was no history
suggestive of fall or any blunt trauma over the abdomen. The patient was on
irregular treatment and had not followed up for 4 years.
Significant
findings on clinical examination were marked pallor, gross abdominal distension
with doughy feel, and forniceal fullness on vaginal examination. She was
referred to us with ultrasonography (USG) suggestive of ill-defined
non-homogenous right adnexal mass lesion and significant free fluid in the
abdomen, raising the possibility of ruptured ectopic pregnancy; hemoglobin of
8.4 g%; white blood cell (WBC) count of 7600/mm3; platelet count of
2.25 lac/mm3; bedside coagulation tests - bleeding time of 2 minutes
40 seconds and clotting time of 4 minutes 50 seconds; and grossly elevated
International Normalized Ratio (INR) of 12.5.
She was
admitted and USG was repeated which suggested a normal sized anteverted uterus
with mild to moderate hemoperitoneum. Urine pregnancy test was negative and
serum βhCG level was < 2 mIU/ml. Repeat investigations on admission revealed
severe anemia with hemoglobin of 5.2 g%, WBC count of 5330/mm3;
platelet count of 3.96 lac/mm3, and INR of 3.58.
Patient
was managed conservatively in consultation with hematologist and gastroenterologist;
accordingly 4 units of Fresh Frozen Plasma (FFP) at the rate of 15ml/kg and 2
units packed cells were transfused. One dose of injection vitamin K 10 mg in
100 ml normal saline was given and further doses of warfarin were withheld.
Tablet azathioprin 100 mg daily was continued along with antibiotics, with
daily monitoring of vital parameters, weight and abdominal girth. General
condition of the patient improved over a period of 6 days, with stable vital
signs, decreasing pain and abdominal girth. Investigations were repeated: USG
showed normal sized anteverted uterus with no evidence of hemoperitoneum,
hemoglobin of 11.2 g%, WBC count of 7300/mm3, platelets of 1.91
lac/mm3, INR of 1.49. Hence she was discharged. The patient was
counseled and anticoagulation was restarted in a dose of 2.5 mg daily at first
follow-up after 15 days. Two months later, flexible sigmoidoscopy was done,
when the intestinal mucosal features were suggestive of remission phase of
ulcerative colitis.
Discussion
The two
most important determinants in warfarin induced bleeding are the intensity of
therapy and maximal time in the therapeutic range. Chances of bleeding are
higher in patients with more intense therapeutic range (INR between 2.5 to
3.5), than in patients with less intense therapeutic range (INR between 2 to
3).[3] This is consistent with the findings in our case where the
INR levels were 12.5.
As
warfarin is a drug with a narrow therapeutic index, another management
challenge is dose adjustment in order to achieve targeted INR. Evidence
suggests that there is large inter- and intra- individual variability in
patient’s response to drug administration, due to factors like age, sex, diet,
concurrent illness, drug interactions and variations in the individual genes
(CYP2C9 and VKORC 1). Studies have shown that patients who are homozygous
mutant for CYP2C9*3 and heterozygous mutant for VKORC 1 possess greater
sensitivity to warfarin therapy as compared to conventional dose regimen; hence
dose adjustment is difficult in these patients. Additionally, larger initial
doses of warfarin suppress protein C and S, resulting in over-anticoagulation
and higher rates of bleeding.[4,5]
In our
case where clinical findings raised the suspicion of ruptured ectopic
pregnancy, ultrasonography and βhCG helped to reach a diagnosis. However
studies suggest that computerized tomography scan is the best imaging modality
to diagnose such cases.[6] In conclusion, although uncommon,
spontaneous intraperitoneal bleeding should be considered as a differential
diagnosis in patients on warfarin therapy who present with acute abdominal
pain.
References
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warfarin dose requirements in Indian patients. Pharmacol Rep 2013;65:1375-82.
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Citation
Saxena N, Chauhan AR. Spontaneous Hemoperitoneum Secondary To Warfarin Toxicity. JPGO 2014 Volume 1 Number 7 Available from: http://www.jpgo.org/2014/07/spontaneous-hemoperitoneum-secondary-to.html