Management of surgery, menorrhagia and child-birth for patients with unclassified bleeding disorders: a systematic review of cohort studies

Abstract

Unclassified bleeding disorders account for 2.6% of all new bleeding disorder registrations in the UK. The management of the bleeding phenotype associated with these disorders is poorly described. Systematic review and meta-analysis to determine the bleeding rates associated with tranexamic acid, desmopressin, platelet transfusion, plasma transfusion and recombinant activated factor VII, for patients with unclassified bleeding disorders undergoing surgery, childbirth or with menorrhagia. We searched for randomized controlled trials in MEDLINE, Embase, The Cochrane Central Register of Controlled Trials, PubMed, ISI Web of Science and the Transfusion Evidence Library from inception to 24 February 2020. Wherever appropriate, data were pooled using the metaprop function of STATA. Two studies with 157 participants with unclassified bleeding disorders were identified. The pooled risk of minor bleeding for patients undergoing surgery treated with peri-operative tranexamic acid was 11% (95% confidence interval 3--20%; n = 52; I 2 = 0%); the risk for desmopressin and tranexamic acid in combination was 3% (95% confidence interval 0--7%; n = 71; I 2 = 0%). There were no instances of major bleeding. In one procedure, 1 of 71 (1.4%), treated with a combination of desmopressin and tranexamic acid, the patient had a line-related deep vein thrombosis. There were too few patients treated to prevent postpartum haemorrhage or for menorrhagia to draw conclusions. The GRADE quality of evidence was very low suggesting considerable uncertainty over the results. However, both tranexamic acid, and the combination of tranexamic and desmopressin have high rates of haemostatic efficacy and have few adverse events. Protocol registration PROSPERO CRD42020169727.

Outcomes and management of pregnancy in women with bleeding disorder of unknown cause

“…We cannot exclude bias from “regression to the mean” whereby women who previously had bleeding events were diagnosed with BDUC and in subsequent pregnancies their risk of PPH regressed to (lower) baseline levels making TXA appear efficacious. While the combination of TXA with desmopressin has been previously reported as efficacious in those with BDUC undergoing surgery we cannot make any generalizations about this in our cohort; however, we may consider it for high bleeding risk cases 26 . There have been no randomized control trials of desmopressin in pregnancy with safety concerns such as maternal/neonatal hyponatremia and the complications of an oxytocic effect of the uterus such as pre‐eclampsia or increased risk of miscarriage 27 .…”

“…While the combination of TXA with desmopressin has been previously reported as efficacious in those with BDUC undergoing surgery we cannot make any generalizations about this in our cohort; however, we may consider it for high bleeding risk cases. 26 There have been no randomized control trials of desmopressin in pregnancy with safety concerns such as maternal/neonatal hyponatremia and the complications of an oxytocic effect of the uterus such as pre-eclampsia or increased risk of miscarriage. 27 A number of studies, however, report on the ante partum and peri partum use of desmopressin in pregnancy without the occurrence of any adverse events.…”

A Unique Case of Post-Biopsy Bleeding in a Jehovah’s Witness with a Rare Inherited Undetermined Coagulopathy

“…In patients with rare bleeding disorders, coordinated management is important to prevent significant bleeding events requiring hospitalization. 8 – 9 Although management and monitoring are not defined clearly in patients with undetermined coagulopathies, and especially those who are Jehovah’s Witnesses, close follow-up and perioperative hemostatic management plans need to be in place to prevent complications. Patients also must be aware of the serious nature of their disease in events of spontaneous or provoked bleeding and must inform healthcare personnel of this issue for proper management.…”

“…1,3,4 However, in patients with rare bleeding disorders where incidence is as low as 1-2 per million, there is not a clear consensus on management of bleeding and especially in those patients who decline blood products for religious reasons. [3][4][5][6][7][8][9][10] Management of GI bleeding is important for these patients as untreated bleeding can result in hemodynamic instability, and treatment with replacement blood and hemostatic agents can cause volume overload and the associated cardiac and renal sequelae. [3][4] Patients with rare bleeding disorders require integrative management between primary care providers, surgeons, and hematologists for best management and prevention of bleeding events requiring hospitalization.…”

Current practice and registration patterns among United Kingdom Haemophilia Centre Doctors’ Organisation centers for patients with unclassified bleeding disorders

“…[1][2][3] Previously, four cases series describing management of UBD patients undergoing invasive procedures has been published with successful use of tranexamic acid and/or desmopressin; however, the quality of evidence is very low. 2,[4][5][6][7] In this study the United Kingdom Haemophilia Centre Doctors' Organisation (UKHCDO; the network of National Health Service [NHS] hospitals that manages patients with bleeding disorders) UBD working party aimed to investigate registration patterns for UBD and clinical practice via a survey of member hemophilia centers to give contemporary real-world data within this area. The working party is composed of hematology clinical scientists and hematologists from within Great Britain and Ireland.…”