Persistent hiccups in a patient with mild congenital factor V deficiency and COVID‐19; clinical and laboratory finding of a rare bleeding disorder

Coronavirus Disease-19 (COVID-19), currently, is the most challenging medical condition in the world. Severity of the infection is variable, ranging from asymptomatic to severe, critical, and life-threatening. A broad range of clinical presentations may occur in patients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including fever, headache, cough, shortness of breath, malaise, and respiratory distress.1 Severity of the infection and mortality rate are higher in those with underlying risk factors such as diabetes, cardiovascular disease, and renal and hepatic failure.2 The infection appears to have a more favorable outcome in patients affected by congenital bleeding disorders (CBDs): COVID-19 and CBDs appear to have a reciprocal effect on each other.3-5 COVID-19 might decrease the bleeding tendency, and CBDs might attenuate hypercoagulability of COVID-19.3 Various clinical presentations were observed in patients with CBDs and COVID-19.3, 6 Here, we reported the first case with congenital factor V (FV) deficiency and COVID-19, presenting with persistent hiccups. A 52-year-old man with a history of diabetes was referred with persistent hiccups (>48 hours). Blood pressure was 137/78 on arrival. Since he was a known patient with mild congenital FV deficiency (FV:C = 35%), he was referred to the hematologist, who conducted routine tests. These included complete blood count (CBC) (Sysmex kx_21 haematology analyser), fasting blood glucose (FBS), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), (Mindray chemistry analyzer, BS-200), C-reactive protein (CRP) (immunoturbidimetry), Antithyroid peroxidase (Anti-TPO), thyroid-stimulating hormone (TSH), T3, and T4 (ELISA kits, Pishtaz Teb) Table 1. Due to the pandemic, a positive CRP, and a decreased platelet count compared to the last platelet count (192 × 109/L vs 385 × 109/L), further assessments for SARS-CoV-2 infection were performed by reverse transcriptase–polymerase chain reaction (RT-PCR) that led to diagnosis of SARS-CoV-2 infection. In the chest computed tomography (CT), ground-glass opacities were observed in the left lower lobe (LLL). Metoclopramide and Chlorpromazine were administered to manage hiccups. While Metoclopramide transiently (<2 hours) decreased the hiccups, Chlorpromazine was more effective. Due to the absence of other signs and symptoms of COVID-19, home isolation with some supportive care, including vitamin C, Vitamin B12, and B complex, was recommended. The rate of hiccups decreased significantly the following day and disappeared entirely 5 days after onset of administration of Chlorpromazine (25 mg PO q6-8hr). At first day, the patient experienced two episodes of epistaxis probably due to severe hiccups, which were controlled by band pressure. As the hiccups ceased, so did the patient's bleeding. SARS-CoV-2 infection, which has variable effects on a patient's life, has numerous clinical presentations.1 Common clinical presentations, such as fever, cough, and shortness of breath, are straightforward and help to better and timely diagnosis, while rarely reported presentations, like hiccups,7 could lead to misdiagnosis and the wrong work-up toward a more serious disorder. Persistent hiccups have been observed only rarely in patients infected by SARS-CoV-2.7 Familiarity with such an extremely rare presentation can help to diagnose COVID-19 not only in patients with CBDs, but also in others. By increasing the pressure on a patient's upper limbs and diaphragm, severe persistent hiccups could increase the bleeding tendency. In this case, the severe persistent hiccups might have trigger epistaxis by this mechanism. Patients with mild congenital FV deficiency are asymptomatic and may experience only trauma-related bleeding8, 9; pressure from hiccups might increase the bleeding tendency. Severe cough in a patient with severe congenital FXIII deficiency under on-demand therapy has been observed to cause severe bleeding.10 It should be considered that bleeding tendency is generally more severe in FXIII deficiency than in FV deficiency, and our patient had a mild reduction of FV levels, with less probability of trauma-related bleeding. Control of such COVID-19 related symptoms in patients with CBDs is crucial in order to decrease unwanted bleeding episodes. Although it seems that SARS-CoV-2 infection does not increase bleeding tendency in patients with CBDs,3 related signs and symptoms that impose some physical pressure on the body could increase bleeding events, potentially severe. Patients affected by CBDs, particularly the severe forms, face the constant threat of bleeding,9 which may be life-threatening. Familiarity with unusual signs of COVID-19 not only can help in timely management of the illness, but also further reduce the potential triggers of bleeding. We highly appreciate Daisy Morant's valuable work in improving the English language of the manuscript. This study was approved by Shahid Beheshti University of Medical Sciences. The authors have no competing interests. A. Dorgalaleh designed the work, performed laboratory analysis, and wrote the manuscript. A. Dabbagh performed clinical studies. Sh. Tabibian, and H. Rafeemehr and M. Bahraini performed laboratory analysis and revised the manuscript. All the authors approved the submission.