The incidence of dengue is rising in many countries and it remains a life threatening illness in the tropics. During dengue epidemics, large numbers of patients (approximately thousands) in all age groups are affected. The natural course of illness and the management approach can be complicated by underlying co-morbidities of patients.
As mentioned previously, this patient’s management during the critical or ‘leakage’ phase of the illness was complicated by two conflicting life threatening conditions; a) risk of massive internal haemorrhage or an intracranial bleed due to dengue induced thrombocytopaenia and b) the need to continue warfarin therapy to avoid a valve thrombosis of the prosthetic mitral valve. Given the lack of emergency cardiothoracic surgical facilities, a valve thrombosis could have been fatal in this patient. Therefore, withholding warfarin was a precarious balancing act to allow just enough time for the thrombocytopaenia to recover and not too long for the valve to thrombose. Decision making was further complicated by the long half life of warfarin. In the absence of guidelines or even published case reports in this regard, it was arbitrarily decided that the risk of bleeding would be significant when the platelet count dropped below 50,000/μl (a cut off value when procedures such as lumbar puncture and organ biopsies are contraindicated in thrombocytopaenic patients). Warfarin had to be stopped well before this mark. It is difficult to predict the rate of drop in platelet count in dengue as in some patients it drops drastically during the critical phase. Adding to the confusion, the critical phase is not synonymous with the period of rapid platelet drop. In other words, the platelet count may continue to fall or fail to rise even after the critical phase is over. Critical phase is only a surrogate marker for the period of rapid platelet drop. The critical / leakage phase is more correctly recognized by presence of a pleural effusion or ascites (clinically or radiologically) . It is assumed that when the platelet count drops below 100,000/μl, the patient will go in to the leakage (critical) phase in the next 24 hours. Taking all in to account, we stopped warfarin when the platelet count approached 100,000/μl and anticipated an interval of at least 48 hours before it dropped below 50,000/μl. The predictions were reasonably accurate and gave us the expected time window for the action of warfarin to wear off.
Prophylactic platelet transfusions are not recommended in dengue as per national guidelines but as the patient developed evidence of active bleeding, we proceeded with transfusions to maintain the platelet count above 20,000/μl. Unexpectedly, the recovery of platelet count did not follow once the patient came out of the critical/leakage phase. It persistently hovered around 20,000-30,000/μl exceeding the 50,000/μl mark only at day 11. Warfarin was withheld till then. We preferred the platelet count to be above 100,000/μl to restart warfarin but already 10 days had lapsed without anticoagulation.
There are no case reports in published literature to our knowledge describing the experience in managing a patient with severe dengue who was also on anticoagulation after a prosthetic cardiac valve insertion (search in Pubmed with keywords ‘dengue’ and ‘anticoagulation’ or ‘warfarin’ in any field). The only case report describing a similar dilemma is by Dan et al. who describe a patient developing portal vein thrombosis following a laparoscopic cholecystectomy whose anticoagulation had to be delayed due to a concurrent dengue infection . In that patient, the platelet count reached a nadir of 16,000/μl and anticoagulation was withheld for 6 days since the diagnosis of the portal vein thrombosis until the platelet count reached 125,000/μl. At that point, the patient was anticoagulated with low molecular weight heparin and later converted to warfarin.
The critical question raised by this experience is exactly how long can a person on mandatory anticoagulation for a prosthetic heart valve can be off warfarin without having a valve thrombosis. Clearly we cannot answer it in relation to dengue patients due to lack of data but indirect evidence can be drawn by experiences with patients having intracranial haemorrhages who were on warfarin [4, 5]. Even then, there are only expert recommendations (no trial evidence) that suggest restarting anticoagulation within 3–10 days in patients whose anticoagulation is mandatory .