Warfarin-Induced Limb Contusion and Haematoma
Correspondence Address :
Dr. Anushree Deshpande,
Assistant Professor, Department of Pharmacy Practice, KLE College of Pharmacy, KAHER, Belagavi-590010, Karnataka, India.
E-mail: anushreedeshpande@klepharm.edu
Warfarin is a narrow therapeutic index drug with high potential to cause adverse effects. It is generally a preferred drug for the management of venous thrombosis. This case is an unusual presentation of left arm contusion and limb haematoma secondary to long-term warfarin use. A 32-year-old male patient was admitted with the complaints of left lower limb oedema and left upper arm oedema. He was on warfarin for dural sinus thrombosis for two years. The integrative analysis of patient clinical presentation, medication history, International Normalised Ratio (INR) level, Ultrasonography (USG) scan and Naranjo assessment showed the probable case of warfarin-induced left arm contusion and limb haematoma. The patient was successively managed with the administration of vitamin K, injection heparin, packed red blood cell and other supportive therapy after the withdrawal of the culprit drug. Thus, patients prescribed with warfarin should be looked at for this typical adverse event. Monitoring of anticoagulant therapy is vital for the positive clinical outcome and minimisation of adverse events. Clinical pharmacists have a key role to play in the patient safety and their inputs can fertilise the concept of pharmacist led anticoagulation clinic in India.
Adverse drug reaction, Anticoagulant, Naranjo assessment
A 32-year-old male patient was admitted with the complaints of left lower limb (Table/Fig 1) and left upper arm tenderness with pitting type oedema type oedema (Table/Fig 2) for 10 days. He had also experienced pain in right hypochondriac region from past seven days which was associated with generalised weakness and muscle cramps. The patient was chronic alcoholic (400 mL/week) over the past 10 years. Based on the Cut down, Annoyed, Guilty, and Eye-opener (CAGE) questionnaire, his drinking habit was categorised as ‘hazardous’. He even regularly chewed tobacco. However, he had quit these habits two years back when he was diagnosed with dural sinus venous thrombosis and was treated with warfarin 5 mg OD and epoetin 100 mg OD.
On physical examination, pallor and soft tenderness in right upper quadrant of the abdomen was observed. The laboratory test of the patient during the hospital stay is depicted in (Table/Fig 3). USG scan was performed on left arm and left foot which revealed a diffused subcutaneous oedema involving deltoid muscle of the left arm, whereas the left foot demonstrated well-defined hypoechoic area on dorsum in subcutaneous plane with no internal vascularity suggesting a haematoma. A USG abdomen scan concluded fatty liver. After correlating the present complaints, past medical history, laboratory investigation and USG scan reports the patient was diagnosed with left arm contusion and left foot haematoma secondary to warfarin therapy. Naranjo adverse drug reaction probability assessment scale was used to classify this Adverse Drug Reaction (ADR) as probable with a score of +6 (Table/Fig 4).
The primary treatment objectives were to reverse the warfarin overdose and resolve or evacuate haematoma. Following the diagnosis, his anticoagulation was reversed with vitamin K 10 mg OD, he was subsequently prescribed with injection pantoprazole 40 mg OD, injection ondansetron 4 mg OD as he complained of vomiting on the second day, injection iron sucrose 100 mg on day 1. On day 2 syrup lactulose 15 mL TID for prophylaxis of hepatic encephalopathy, tablet chymotrypsin BID for prophylaxis of i.v. cannula related swelling, injection tramadol SOS and on day 3, he was given injection amoxycillin and potassium clavulanate 625 mg BID, injection heparin 5000 units BID. He was administered with 5 units of packed red blood cells on day 2, day 4, day 6 and day 12. All these treatments continued and on the thirteenth day, INR levels and haemoglobin were found to be 1.3 and 9.1 mg/dL, respectively. The patient was advised for surgery to evacuate the haematoma but he declined due to financial constraints and took discharge against medical advice.
On discharge, rivaroxaban 10 mg OD, chymotrypsin TID, amoxicillin plus potassium clavulanate 625 mg BID for five days were prescribed. The patient was educated about warfarin-related adverse reactions along with a yellow card. At the time of discharge, the INR level was stabilised to 1.3 and was advised to follow-up after one month.
Cerebral dural sinus venous thrombosis is one of subtypes of venous thrombosis accounting for 30% of all strokes in India and primarily caused by the high levels of pro-coagulants, which may be associated with inherited thrombophilia. Presently available treatment options include anti-thrombotic therapy with heparin and oral anticoagulants like warfarin (1). Similarly, in this case, the patient was treated with warfarin 5 mg over a period of two years. It interferes with coagulation pathways by inhibiting Vitamin K Epoxide Reductase Complex 1 (VKORC 1) leading to decline in biosynthesis of vitamin K dependent pro-coagulants (2). The pharmacodynamic response of warfarin is uncertain due to the influence of genetic polymorphism of VKORC1 and CYP2C9 which plays a key role in warfarin metabolism. In some individual’s, coagulopathy develops rapidly due to previously existing factor VII deficiencies (3). Warfarin-related adverse events such as bleeding are frequently reported by patients.
Moreover, any trauma can rupture the blood vessel, forming a contusion that appears like bruises and further when the same blood leaks into a tissue compartment it forms a haematoma (4). Some of the rare haematomas are reported in locations like intraspinal, gastric intramural, retropharyngeal and iliopsoas region (5). This case report focuses on limb haematoma, an unusual location for haematoma. Patients on long-term warfarin therapy require INR monitoring between 2 to 3, as slight change in diet, compliance to therapy, disease, age or a patient’s response to drug might cause fluctuations in INR levels. However, haematomas are also reported between 2 to 3 therapeutic INR levels (6).
Similarly, in this patient the INR levels at the time of admission were 2.39. Drug induced haematoma are generally observed among the patients prescribed with anticoagulants (warfarin), antiplatelets (aspirin, dipyridamole, clopidogrel) (7). Additionally, Aspirin and related phenolic drugs are also reported to cause life-threatening drug reactions called pemphigus (8). There are no guidelines for diagnosis of warfarin associated adverse reaction, however this case was diagnosed based on clinical presentation, past medication history and USG scan which directly points towards haematoma secondary to warfarin therapy. The management strategies for warfarin related ADR requires attaining the INR levels below 2. This can be achieved by termination of warfarin therapy, administration of vitamin K, prothrombin complex concentrator and fresh frozen plasma in case of fatal bleeding (9). A case series reported the dose of vitamin K can vary from 10 mg to 50 mg and maximum up to 110 mg (10). Thus, treatment plan in this patient correlated with the standard treatment strategy. Patients are also transfused with fresh frozen plasma (11). Alternatively, this patient was transfused with packed red cells to correct the haematological parameters.
The administration of warfarin therapy and achieving stable INR levels in Cerebral Venous Thrombosis (CVT) is a challenging task and sometimes leads to complications like haemorrhage and formation of haematoma. However, warfarin nomogram can aid in appropriately adjusting the dose based on target INR level the dose can range from 5 mg to 12.5 mg (12). About 6.7% of total hospital admission is due to serious adverse drug reactions, further adding healthcare cost and financial burden on patients (13). However, a multicentred study found that direct oral anticoagulants like rivaroxaban and dabigatran are safer and efficacious when compared to warfarin in the treatment of Cerebral Venous Thrombosis (CVT). Although, Direct Oral AntiCoagulants (DOACs) do not necessitate INR monitoring, they typically are more expensive than warfarin and lack information on cost-effectiveness among CVT patients (14). Therefore, by substituting brand drugs by generic medicine can minimise healthcare cost due to medication (15).
Haematoma in the limbs resulting from warfarin overdose is rare but a serious adverse reaction which can affect the patient’s mobility. Thus, patients on warfarin should be properly monitored for this adverse effect. Clinical pharmacist could play a significant role in the detection of such rare events and suggest a better therapeutic approach which might give birth to the concept of pharmacist led anticoagulation clinics where patient can be educated about the INR level, anticoagulants, its side effects, interactions and encourage consumer to self-report drug allergies.
We would like to thank our Prinicipal, KLE College of Pharmacy, Belagavi for encouragement and also thank Dr. Deepthi Avvaru for her constant support during this work.
DOI: 10.7860/JCDR/2023/60428.17905
Date of Submission: Sep 24, 2022
Date of Peer Review: Nov 15, 2022
Date of Acceptance: Jan 10, 2023
Date of Publishing: Apr 01, 2023
AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. Yes
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