Oral Anti-Coagulant (Acitrom) Induced Coagulopathy - A Case Report

Introduction

A large number of 4-hydroxycoumarins, with aromatic substituent at the 3’ position, possess anticoagulant properties and collectively called coumarinic oral anticoagulants (COAs). The commercially available coumarins are Warfarin, Acitrom, Acenocoumarol and Phenprocoumon. In India, Acitrom is the popular drug of choice for oral anticoagulant therapy with multiple indications. In various other parts of the world, Warfarin is used as an oral anticoagulant. Both the drugs, Acitrom and Warfarin are part of the Acenocoumarol drug class, and are available in R- and S- enantiomeric forms.¹ Though Acenocoumarol (Acitrom) and Warfarin belong to the same class, Acitrom has a greater half-life and fewer interactions than Warfarin.

These agents are Vitamin K antagonists (VKAs) and work by inhibiting the action of the enzyme, Vitamin K epoxide reductase which is necessary for the activation of vitamin K-dependent coagulation factors II, VII, IX, X and regulatory proteins C, S, and Z. This enzyme is also essential for the regeneration and in maintaining the required levels of Vitamin K for blood clotting.² While Coumarins play a major role in the prevention and treatment of venous and arterial thrombosis, it can still cause bleeding (especially if overdosed), or thrombosis (especially if underdosed). To minimize the risk of these complications, the prothrombin time (PT) - generally expressed as the International Normalized Ratio (INR) to allow comparability among canters is used to monitor the degree of coumarin-associated anticoagulation. A normal INR is between 0.8 and 1.2. font in this page looks different than others, kindly cross check, but is typically between 2.0 and 3.5. An INR of less than 2.0 is associated with greater risk for thromboembolic events, while an INR of greater than 4.0 is associated with increased risk of bleeding.³ Acitrom and Warfarin therapy can result in major bleeding complications due to a narrow therapeutic index, an unpredictable biological response and multiple interactions with concomitant drugs, food and other patient-related factors. For patients receiving a stable dose of oral anticoagulants, monitoring at an interval no longer than four weeks is suggested.¹

Case Presentation

A 50-year-old male patient presented with a complaint of ecchymosis over abdomen and thigh (Figure 1) and hematuria since five days. Patient underwent an open heart surgery 20 years back and was on T. Acitrom 4 mg since then. On examination, BP was 120/60 mmHg, PR was 100 bpm, SPO₂ was 98%, reducing at room temperature. On systemic examination, respiratory system - B/L NVBS (+), no added sounds, CNS - Conscious and oriented, CVS - S1 S2 heard, no murmur, P/A - soft, non-tender, no organomegaly. The patient was a non-alcoholic and non-smoker.

On physical examination, ecchymosis over abdomen and thigh (due to T. Acitrom- 4 mg) were noted and laboratory investigation revealed hemoglobin value of 11.5 gm/dL, platelet count was 2.90 lakh/cu mm, WBC count was 6600, prothrombin time was 59.9 seconds and INR was 5.9. The doppler study of right upper limb (arterial) showed mildly hyperechoic thrombus in mid axillary artery with dampened monophasic f low in bilateral, radial and ulnar arteries; S/o chronic thrombosis. Based on the above-mentioned details, a diagnosis of ‘Acitrom Induced Coagulopathy’ was made and the patient was advised to stop taking T. Acitrom 4 mg. A treatment plan was devised with Inj. Tranxamic acid 500 mg (SOS), Inj. Vitamin K 2 cc (stat), Inj. Pantoprazole 40 mg (1-0-0), and transfusion of four pint fresh frozen plasma; this treatment was continued for four days.

This case was analyzed using Naranjo Scale, WHO Causality Assessment Scale, Karch and Lasagna Scale. According to Naranjo Scale, algorithm was six which is characterized as ‘probable reaction’ and as per WHO Casualty Assessment Scale, patient was categorized under ‘probable’ and the Karch and Lasagna Scale suggested a ‘possible reaction’. On the basis of these scales, this case was concluded as ‘Acitrom induced coagulopathy’.

Discussion

For decades, Warfarin, Acitrom or oral Vitamin K antagonists were the most common anticoagulants used. However, with the narrow therapeutic index and multiple drug and food interactions associated with Warfarin, an alternative was needed. Warfarin, a coumarin derivative works as an anticoagulant by preventing the adherence of platelets to form a blood clot. However, regular monitoring (INR monitoring) is necessary as it may cause serious bleeding.³

To treat a bleeding that can be life threatening, the following three steps must be followed:

1. Withholding of anticoagulants is required to avoid further bleeding. Withholding can only result in a slow reduction of INR value. 
2. Administration of Vitamin K in the intravenous route results in rapid onset when compared to the oral route. Vitamin K injection (5 mg) is useful for complete correction in majority of the situations. 
3. In major life-threatening conditions, coagulation factors need to be replaced. This can be achieved by the administration of fresh frozen plasma and prothrombin complex concentrate.²

In the present case, the patient presented with ecchymosis over the abdomen and thigh region and hematuria was noted since five days. Patient underwent an open-heart surgery 20 years back and was on T. Acitrom 4 mg since then. The suspected drug for causing the reddish pigmentation was Acitrom. The patient was advised to stop taking T. Acitrom 4 mg and instead was advised T. Acitrom 3 mg to be taken at 6 pm for one week. A treatment plan was devised with Inj. Tranxamic acid 500 mg (SOS), Inj. Vitamin K 2 cc (stat), Inj.

Pantoprazole 40 mg (1-0-0), and transfusion of four pint fresh frozen plasma; this treatment was continued for four days.

In this presented scenario, as clinical pharmacists, we identified the cause for the occurred reaction as Acitrom. Acitrom was immediately withdrawn and the patient was provided with appropriate treatment for prompt recovery.

Acenocoumarol (Acitrom), an oral anti-coagulant, is similar to Warfarin but has a longer half-life and fewer interactions. It is available in dosages of 1, 2 and 4 mg in tablet form. As many as forty adverse effects of Warfarin have been reported, with bleeding being the most common and potentially most dangerous if not promptly treated. Here we report a rare case of Acitrom induced coagulopathy in a 50 year old male patient which was effectively managed to avoid morbidity and mortality associated with Acitrom toxicity. The patients receiving Acitrom should be advised to report any accidents, injuries and any signs and symptoms of bleeding or unusual bruising. It is of utmost significance to monitor and normalize INR levels.

Patient Perspective

During admission, the patient was nervous and clueless regarding the ecchymosis formation on his body. Later, after the treatment was initiated, positive results were observed and the patient was able to overcome ecchymosis. We humbly thank the medical teams for helping him recover.

Patient Consent

Written informed consent was obtained from the patient for publication of this case report and accompanying images.

Declaration of Competing Interest

No conflict of Interest