Management of pregnancy in dysfibrinogenemia cases: a dilemma.

Dysfibrinogenemia is a very challenging disorder, and there are no firm guidelines on treatment for pregnant patients with dysfibrinogenemia. A 37-year-old patient with a history of six unexplained recurrent miscarriages was referred for thrombophilia testing. Elevated procoagulant microparticles were found, for which during her seventh pregnancy anticoagulant therapy was initiated. However, she again miscarried and bled excessively. She was then diagnosed with dysfibrinogenemia. DNA sequence analysis revealed a novel homozygous insertion-deletion in exon 7 in FGB. Dysfibrinogenemia is very difficult to diagnose and even after diagnosis, the treatment varies with the patient's symptoms. In this case, anticoagulant therapy failed. With her history of recurrent miscarriages, it is clear that pregnancy without any treatment is not an option. Few reports suggest a combination of intravenous fibrinogen infusions along with anticoagulants in which successful pregnancy outcome was achieved. The present case thus stresses on the need for some treatment guidelines in such cases.

Paradoxical bleeding and thrombosis in a patient with afibrinogenemia and fibrinogen Mumbai mutation.

OBJECTIVES: Thrombosis is rarely reported in cases of afibrinogenemia and is generally associated with thrombophilia or replacement therapy. Often, it is difficult to predict whether the patients will bleed or whether they are exposed to the risk of thrombosis. METHODS: We report a patient with afibrinogenemia who presented with complete thrombosis of right hepatic, portal, and splenic veins and who described a lifelong history of bleeding. Direct sequencing of the three fibrinogen genes was performed to identify the mutation. RESULTS: DNA sequencing showed the presence of a homozygous for G8017A substitution in exon 8 of the fibrinogen ß-chain gene, resulting in a G434D missense mutation (Fibrinogen Mumbai). CONCLUSIONS: Presence of both bleeding and thrombotic manifestations in a patient with afibrinogenemia in the presence of other associated risk factors warrants a very careful individualized approach in the management of patients with afibrinogenemia.

The Epidemiology of FVIII Inhibitors in Indian Haemophilia A Patients.

A serious complication of replacement therapy in patients with bleeding disorders is the development of 'inhibitors', particularly FVIII inhibitors in haemophilia A patients. This leads to an increase in the management cost, morbidity and mortality, especially post-operatively. The mechanism of FVIII inhibitor development is quite complex and it is difficult to predict inhibitor development, but a prompt and accurate diagnosis is critical as early therapy can save lives. The aim of this study was to screen patients with bleeding disorders in India for inhibitors, and to analyse and compare the prevalence of inhibitors in different regions in India. Patient details were recorded and blood samples were collected in sodium citrate vacutainers from 1,505 patients with bleeding disorders, in different cities in India. Coagulation and inhibitor screening assays were performed, followed by the Bethesda assay in inhibitor positive samples to quantify the FVIII inhibitor titre. Out of the 1,505 samples analysed, 1,285 were Haemophilia A patients, out of which 78 (6.07 %) were positive for 'FVIII Inhibitors'. The highest incidence of FVIII Inhibitors was seen in South India (13.04 %). The highest incidence of 20.99 % was observed in Chennai, followed by Hyderabad (13.33 %), Jammu (9.90 %) and Guwahati (8.51 %), respectively, with respect to the samples analysed. The other regions showed an inhibitor incidence <8 %. The incidence of inhibitors in haemophilia A patients is different in different regions of India; this may be due to the intensity of treatment, type of product or the genetic characteristics of these patients.