A British Society for Haematology Guideline: Diagnosis and management of thrombotic thrombocytopenic purpura and thrombotic microangiopathies.

The objective of this guideline is to provide healthcare professionals with clear, up-to-date and practical guidance on the management of thrombotic thrombocytopenic purpura (TTP) and related thrombotic microangiopathies (TMAs), including complement-mediated haemolytic uraemic syndrome (CM HUS); these are defined by thrombocytopenia, microangiopathic haemolytic anaemia (MAHA) and small vessel thrombosis. Within England, all TTP cases should be managed within designated regional centres as per NHSE commissioning for highly specialised services.

A British Society for haematology guideline: diagnosis and management of thrombotic thrombocytopenic purpura and thrombotic microangiopathies

The objective of this guideline is to provide healthcare professionals with clear, up-to-date and practical guidance on the management of thrombotic thrombocytopenic purpura (TTP) and related thrombotic microangiopathies (TMAs), including complement-mediated haemolytic uraemic syndrome (CM HUS); these are defined by thrombocytopenia, microangiopathic haemolytic anaemia (MAHA) and small vessel thrombosis. Within England, all TTP cases should be managed within designated regional centres as per NHSE commissioning for highly specialised services.

Unclassified bleeding disorders: outcome of haemostatic challenges following tranexamic acid and/or desmopressin.

INTRODUCTION: In a minority of patients with a significant bleeding history no cause is found despite extensive testing and we diagnose such cases as unclassified bleeding disorders (UBD). UBDs may have diverse underlying causes and currently no standard management strategy exists in the event of a haemorrhage or to cover surgery. AIM: To document the clinical characteristics and response to treatment of UBDs. METHODS: We performed a retrospective chart review of all patients with UBDs who had an invasive procedure at our centre between 1998 and 2014. RESULTS: The commonest symptoms were menorrhagia (89%) and bleeding at the time of surgery (88%) or dental extraction (85%). A total of 33 patients underwent 78 minor and major haemostatic challenges. Haemostatic cover was provided in 28 procedures with tranexamic acid alone, two with desmopressin and 45 with both agents in combination. A successful haemostatic outcome was observed in 70/78 (90%) cases. No patient required additional surgical intervention to achieve haemostasis, but one patient required a platelet transfusion to control postoperative bleeding. CONCLUSIONS: This is the first study to report on the investigation and treatment of UBD. Future studies are needed to further our understanding of the bleeding phenotype and identify any underlying causes.

National audit of the use of fibrinogen concentrate to correct hypofibrinogenaemia.

BACKGROUND: Massive haemorrhage occurs in a variety of clinical settings resulting in consumptive and dilutional coagulopathies leading to hypofibrinogenaemia. METHODS/MATERIALS: A prospective observational national cohort study was performed between November 2008 and June 2010 to collect safety data on the off-label use of a fibrinogen concentrate to treat acquired hypofibrinogenaemia. RESULTS: A prospective cohort of 63 patients with varying causes of hypofibrinogenaemia resulted from this data collection. A single infusion of fibrinogen concentrate was given in 49 (77%) of patients studied and 12 received more than one infusion. The median inter-quartile range (IQR) dose of fibrinogen infused was 49 (26-61) mg kg(-1). The median (IQR) fibrinogen level before and after infusion was 0.9 (0.6-1.3) and 1.8 (1.4-4.3) g L(-1), respectively (P < 0.001). In 31 patients (67%), bleeding stopped within 4 h and fibrinogen was reported to have contributed to this outcome by the treating clinicians. In 84% of cases the treating clinician reported that the use of fibrinogen concentrate reduced the rate of bleeding. Fibrinogen was associated with a statistically significant reduction in red blood cell transfusion (median 4 units before and 0 units after, P < 0.001) and fresh frozen plasma infusion (median 4 units before and 0 units after, P < 0.001). Three venous and one arterial non-fatal thrombotic events were recorded in the patients treated with fibrinogen. CONCLUSION: Fibrinogen concentrate can be used to correct hypofibrinogenaemia and may reduce blood product usage.

Standard haemostatic tests following major obstetric haemorrhage.

BACKGROUND: Postpartum haemorrhage is an important cause of maternal morbidity and mortality. It is associated with haemostatic impairment which may exacerbate bleeding. METHODS: All deliveries over a 3-year period in a large UK unit were reviewed and cases of haemorrhage of 1500 mL or more identified. Laboratory records were reviewed and the lowest value for haemoglobin, platelet count and fibrinogen, and longest value for prothrombin time and activated partial thromboplastin time within 24h of delivery were recorded. RESULTS: Of 18,501 deliveries there were 456 bleeds of 1500 mL or more (2.5%). Fibrinogen levels correlated best with blood loss (r -0.48 P<0.01) and fell progressively as volume increased. Activated partial thromboplastin time was less sensitive (r 0.4 P<0.01) to increasing blood loss. Prothrombin time did not correlate with blood loss (r 0.01). Activated partial thromboplastin time and prothrombin time remained within the normal range in most women despite large bleeds. Similar results were observed in women who received four or more units of red blood cells. Haemoglobin level was adequately maintained irrespective of blood loss. Based on UK national guidelines only 13 of 456 (3%) women should have received fresh frozen plasma, although it was given to 45; despite this, fibrinogen levels below the pregnancy-related normal range were observed in most cases. CONCLUSION: Fibrinogen level was the parameter that best correlated with increasing volume of haemorrhage and was the most useful marker of developing haemostatic impairment. Guidelines for fresh frozen plasma use in major postpartum haemorrhage were rarely followed and should be reviewed.

The use of fibrinogen concentrate to correct hypofibrinogenaemia rapidly during obstetric haemorrhage.

Haemorrhage is a common complication of childbirth with 0.65% of deliveries associated with significant (>1500 mL) peripartum blood loss. Hypofibrinogenaemia secondary to dilutional and consumptive coagulopathies can be challenging to correct quickly with conventional blood and plasma therapy. Fibrinogen concentrate offers rapid restoration of fibrinogen levels with a small volume infusion and minimal preparation time. It is effective in treating patients with congenital hypofibrinogenaemia, but there are few reports of its use in association with continuing obstetric haemorrhage. Six cases of obstetric haemorrhage, associated with hypofibrinogenaemia, treated with fibrinogen concentrate in conjunction with platelets, fresh frozen plasma, packed red blood cells, uterotonics and obstetric intervention are described. In all cases, laboratory assessed coagulation was rapidly normalised and severe haemorrhage improved. These cases suggest that fibrinogen concentrate may be an effective addition to conventional treatments for obstetric haemorrhage associated with hypofibrinogenaemia.

Antenatal interventions for fetomaternal alloimmune thrombocytopenia.

BACKGROUND: Fetomaternal alloimmune thrombocytopenia occurs when the mother produces antibodies against a platelet alloantigen that the fetus has inherited from the father. A consequence of this can be a reduced number of platelets (thrombocytopenia) in the fetus, which can result in bleeding whilst in the womb or shortly after birth. In severe cases this bleeding may lead to long-lasting disability or death. Antenatal management of fetomaternal alloimmune thrombocytopenia centres on preventing severe thrombocytopenia in the fetus. Available management options include administration of intravenous immunoglobulins or corticosteroids to the mother or intrauterine transfusion of antigen compatible platelets to the fetus. All options are costly and need to be assessed in terms of potential risk and benefit to both the mother and an individual fetus. OBJECTIVES: To determine the optimal antenatal treatment of fetomaternal alloimmune thrombocytopenia to prevent fetal and neonatal haemorrhage and death. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (February 2004), EMBASE (1980 to February 2004) and bibliographies of relevant publications and review articles. SELECTION CRITERIA: Randomised controlled studies comparing any intervention, including corticosteroids with no treatment, or comparing any two interventions. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed eligibility, trial quality and extracted data. MAIN RESULTS: One study met the inclusion criteria (54 pregnant women). This trial compared intravenous immunoglobulins plus corticosteroid (dexamethasone) with intravenous immunoglobulins alone. No significant differences were reported between the treatment and control groups, in any outcome measured: mean platelet count at birth (weighted mean difference (WMD) 14.10 x 10 9/l, 95% confidence interval (CI) -30.26 to 58.46), mean gestational age at birth (WMD -0.50 weeks, 95% CI -2.69 to 1.69), mean rise in platelet count from first to second fetal blood screen (WMD -3.50 x 10 9/l, 95% CI -24.62 to 17.62) and mean rise in platelet count from birth to first fetal blood screen (WMD 24.40 x 10 9/l (95% CI -14.17 to 62.97)). This trial had adequate methodological quality; however the method used to calculate sample size was inappropriate: therefore the power calculation was not sufficient to determine any significance in differences between the treatment groups. AUTHORS' CONCLUSIONS: There are insufficient data from randomised controlled trials to determine the optimal antenatal management of fetomaternal alloimmune thrombocytopenia. Future trials should consider the dose of intravenous immunoglobulins, the timing of initial treatment, monitoring of response to treatment by fetal blood sampling, laboratory measures to define pregnancies with a high risk of intercranial haemorrhage, management of non-responders and long-term follow up of children.