Platelet storage pool disorder in pregnancy: Utilising thromboelastography to guide a risk-based delivery plan.

We present a case of a 33-year-old woman in her third pregnancy diagnosed with platelet storage pool disorder who had previously suffered two postpartum major obstetric haemorrhages. Platelet storage pool disorder is a rare bleeding disorder where the platelet count is normal but platelet function is impaired due to deficiency of dense granules. A peripartum plan devised by an extensive multi-disciplinary team using principles for managing other bleeding and platelet function disorders helped minimise her risk of major haemorrhage. We also describe how point-of-care thromboelastography can help guide management and enable an individualised risk-benefit discussion with the woman about her anaesthetic choices.

Physician experiences in management of COVID-19-associated coagulopathy in pregnancy: Communication from the ISTH SSC Subcommittee on Women's Health Issues in Thrombosis and Haemostasis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) occurs following infection with the potentially fatal, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. Infection can be complicated by coagulopathy, at times featuring thrombocytopenia and thrombosis alongside other coagulation abnormalities, also termed COVID-19-associated coagulopathy (CAC). Data concerning CAC in pregnancy are limited. Better understanding of physician experiences is essential to identify current practice patterns and knowledge gaps. OBJECTIVES: To determine physician experiences and practice patterns regarding CAC in pregnancy. METHODS: Self-administered survey using the RedCap online platform; supported by the ISTH Subcommittee on Women's Health Issues in Thrombosis and Hemostasis. RESULTS: Seventy-five respondents fully or partially completed the survey. Of 1546 reported cases, disease severity was specified in 1298. Sixty-four percent of COVID-19 infections were mild, whereas 4% were severe. Of all cases, 1% developed CAC, with 65% classified as severe. The most frequent abnormalities included thrombocytopenia, elevated C-reactive protein, D-dimer, and lymphopenia. Low molecular weight heparin was the anticoagulant of choice in CAC and was provided by 77% of respondents, with 60% using standard prophylactic dosing. Thrombosis occurred in seven anticoagulated patients who were receiving standard prophylactic (four) or weight-based (three) dosing. Disease severity and additional thrombosis risk factors dictated anticoagulation duration. CONCLUSION: In the select population reported by our survey, CAC appears to be uncommon in pregnancy. Anticoagulation practices vary and may not reflect current guidelines. Venous thromboembolism was observed in some CAC patients despite prophylactic anticoagulation (including standard and weight-adjusted dosing). Urgent research is required to determine appropriate anticoagulant dosing and duration in pregnant women with COVID-19 infection.

Managing women-specific bleeding in inherited bleeding disorders: A multidisciplinary approach.

INTRODUCTION: Multidisciplinary management of women-specific bleeding is important to preserve quality of life, healthy reproduction and social participation of women and girls with bleeding disorders (WBD). AIM: To support appropriate multidisciplinary care for WBD in haemophilia treatment centres. METHODS: Two case examples are presented and management issues discussed from different health care perspectives, including the nurse, patient, psychologist, gynaecologist, geneticist, psychosexual therapist and haematologist. RESULTS: Woman with bleeding disorders may experience heavy menstruation from menarche onwards. This has a physical and psychosocial impact requiring a multidisciplinary approach. If a woman with an inherited bleeding disorder desires to become pregnant, preconception counselling is essential, to discuss genetic diagnosis, state of the art treatment options for the bleeding disorder in question and possible choices to prevent having an affected child, as well as maternal bleeding risks during conception, delivery and the post-partum period. CONCLUSION: Adequate management and good education of WBD requires a patient-centred multidisciplinary approach with experienced specialists in a haemophilia treatment centre.

Women with inherited bleeding disorders - Challenges and strategies for improved care.

Women with inherited bleeding disorders (IBDs) experience significant challenges in their health, personal and reproductive lives. Heavy menstrual bleeding (HMB), general bleeding symptoms, iron deficiency and excessive bleeding during miscarriage, pregnancy and delivery are all common complications for women with IBDs. Symptoms may present in childhood or adolescence, often with significant delays to definitive diagnosis and appropriate treatment due to lack of recognition of the prevalence and impact of IBDs in women. This can greatly reduce the quality of life of affected girls and women with school and work absence, social embarrassment and self-consciousness being highly prevalent. The impact of being affected by or being a carrier of a genetic disorder can also cause significant psychological distress for women and their partners embarking on a pregnancy. Increased awareness and better understanding of causes and approach for diagnosis of gynaecological bleeding have improved the identification of women who require further haemostatic testing, however many women remain un-diagnosed and un-treated. Education and training of care givers and multi-disciplinary approach are crucial to enable collaborative, patient-centred care including management of bleeding symptoms, haemostatic planning in advance of surgery, pregnancy and delivery and individualised genetics counselling for couples on their reproductive options. This review discusses the current challenges in the care of women with IBDs and strategies to improve their recognition and diagnosis, clinical management and overall quality of life.

Barriers and challenges faced by women with congenital bleeding disorders in Europe: Results of a patient survey conducted by the European Haemophilia Consortium.

INTRODUCTION: Historically, issues faced by women with bleeding disorders (WBD) have been underestimated. While advances in genetic testing have resulted in improvements, significant challenges remain in the initial recognition of abnormal bleeding and referral of WBD. METHODS: The European Haemophilia Consortium (EHC) developed a questionnaire for WBD to provide insights into the barriers and challenges faced by WBD in Europe. RESULTS: In total, 709 WBD responded to the survey from 32 countries, predominantly from western European countries (94%). A delay in ascertaining the diagnosis of a congenital bleeding disorders (CBD) remains, with a median age at diagnosis of 16 years. The presence of family history is strongly associated with a lower median age at diagnosis of 6 years. WBD reported significant disease impact on their day-to-day life, most evident for the rarer CBD. The bleeding symptom of biggest impact on daily life is heavy menstrual bleeding (HMB), reported by 55% of women. Importantly, 25% of WBD reports that their condition severely impacted their decision to have or has prevented them from having children. Respondents registered with Haemophilia Treatment Centres (HTC) are 2.2 times more likely to receive treatment compared to WBD in other hospital services. CONCLUSION: Improved education for both patients and healthcare providers is essential to improve time to diagnosis, access to treatment and psychosocial supports for WBD in Europe.

Congenital Factor X deficiency in women: A systematic review of the literature.

Factor X deficiency (FXD) is a rare autosomal recessive bleeding disorder with a variable phenotypic severity. In women, heavy menstrual bleeding (HMB), recurrent ovulation bleeding with haemoperitoneum and bleeding complications in pregnancy such as retroplacental haematoma and postpartum haemorrhage have been reported. The aim of this review was to examine gynaecological problems and obstetric complications in women with congenital FXD. A total number of 49 relevant articles were identified, including 332 women, dating from 1960 to 2018. Heavy menstrual bleeding was reported in 72/284 (25%) women in total, 14/30 (47%) in case reports and 58/254 (23%) in 11 case series, 64% and 10% required blood products and blood transfusion, respectively. Haemoperitoneum from ovulation bleeding or ruptured haemorrhagic ovarian cyst requiring blood transfusion occurred in 8/322 (2.4%) women, six required surgical intervention, including oophorectomy in two. 31 pregnancies were reported in 19 women. There were four miscarriages (including a late miscarriage at 21 weeks). There was a high rate of preterm birth and neonatal death occurring in eight (30%) and three (11%) of pregnancies reaching viability stage. Postpartum haemorrhage (PPH) occurred in six (22%) of deliveries, one requiring hysterectomy. In conclusion, women with FXD are at an increased risk of heavy bleeding during menstruation and ovulation as well as adverse pregnancy outcome and postpartum haemorrhage. Collaboration in a multidisciplinary team including an obstetrician/gynaecologist, a perinatologist and a haematologist is necessary for the prevention and management of these complications.

Noninvasive detection of F8 int22h-related inversions and sequence variants in maternal plasma of hemophilia carriers.

Direct detection of F8 and F9 sequence variants in maternal plasma of hemophilia carriers has been demonstrated by microfluidics digital PCR. Noninvasive prenatal assessment of the most clinically relevant group of sequence variants among patients with hemophilia, namely, those involving int22h-related inversions disrupting the F8 gene, poses additional challenges because of its molecular complexity. We investigated the use of droplet digital PCR (ddPCR) and targeted massively parallel sequencing (MPS) for maternal plasma DNA analysis to noninvasively determine fetal mutational status in pregnancies at risk for hemophilia. We designed family-specific ddPCR assays to detect causative sequence variants scattered across the F8 and F9 genes. A haplotype-based approach coupled with targeted MPS was applied to deduce fetal genotype by capturing a 7.6-Mb region spanning the F8 gene in carriers with int22h-related inversions. The ddPCR analysis correctly determined fetal hemophilia status in 15 at-risk pregnancies in samples obtained from 8 to 42 weeks of gestation. There were 3 unclassified samples, but no misclassification. Detailed fetal haplotype maps of the F8 gene region involving int22h-related inversions obtained through targeted MPS enabled correct diagnoses of fetal mutational status in 3 hemophilia families. Our data suggest it is feasible to apply targeted MPS to interrogate maternally inherited F8 int22h-related inversions, whereas ddPCR represents an affordable approach for the identification of F8 and F9 sequence variants in maternal plasma. These advancements may bring benefits for the pregnancy management for carriers of hemophilia sequence variants; in particular, the common F8 int22h-related inversions, associated with the most severe clinical phenotype.

Bleeding risk of surgery and its prevention in patients with inherited platelet disorders.

Excessive bleeding at surgery is a feared complication in patients with inherited platelet disorders. However, very few studies have evaluated the frequency of surgical bleeding in these hemorrhagic disorders. We performed a worldwide, multicentric, retrospective study to assess the bleeding complications of surgery, the preventive and therapeutic approaches adopted, and their efficacy in patients with inherited platelet disorders: the Surgery in Platelet disorders And Therapeutic Approach (SPATA) study. We rated the outcome of 829 surgical procedures carried out in 423 patients with well-defined forms of inherited platelet disorders: 238 inherited platelet function disorders and 185 inherited platelet number disorders. Frequency of surgical bleeding was high in patients with inherited platelet disorders (19.7%), with a significantly higher bleeding incidence in inherited platelet function disorders (24.8%) than in inherited platelet number disorders (13.4%). The frequency of bleeding varied according to the type of inherited platelet disorder, with biallelic Bernard Soulier syndrome having the highest occurrence (44.4%). Frequency of bleeding was predicted by a pre-operative World Health Organization bleeding score of 2 or higher. Some types of surgery were associated with a higher bleeding incidence, like cardiovascular and urological surgery. The use of pre-operative pro-hemostatic treatments was associated with a lower bleeding frequency in patients with inherited platelet function disorders but not in inherited platelet number disorders. Desmopressin, alone or with antifibrinolytic agents, was the preventive treatment associated with the lowest bleedings. Platelet transfusions were used more frequently in patients at higher bleeding risk. Surgical bleeding risk in inherited platelet disorders is substantial, especially in inherited platelet function disorders, and bleeding history, type of disorder, type of surgery and female sex are associated with higher bleeding frequency. Prophylactic pre-operative pro-hemostatic treatments appear to be required and are associated with a lower bleeding incidence.

Heavy menstrual bleeding: An update on management.

Heavy menstrual bleeding (HMB) is defined as excessive menstrual blood loss (MBL) >80 mL per cycle, that interferes with a woman's physical, emotional, social wellbeing and quality of life. Aetiology is due to underlying uterine pathologies, coagulopathy, ovulation dysfunction, or iatrogenic. Up to 20% of women with HMB will have an underlying inherited bleeding disorder (IBD). Assessment of HMB should entail a menstrual and gynaecological history and a bleeding score to distinguish those women who require additional haematological investigations. A pelvic examination and ultrasound scan help to rule out presence of any underlying pathology. Management depends on the underlying cause and the woman's preference and her fertility wishes. Medical therapies include hormonal treatments; levonorgestrel-releasing intrauterine system (LNG-IUS) and combined hormonal contraceptives are most commonly used. Ulipristal acetate is an approved preoperative treatment for uterine fibroids, and has demonstrated efficacy in reducing MBL. Haemostatic therapies include tranexamic acid and DDAVP (1-deamino-8-D-arginine). DDAVP is used for HMB associated with certain IBDs. These therapies can be used in isolation or in combination with hormonal treatments. HMB associated with certain severe IBDs may require factor concentrate administration during menses to alleviate symptoms. Endometrial ablation is a minor surgical procedure that is associated with low operative morbidity and can be performed as an outpatient. Hysterectomy remains the definitive treatment of choice when medical therapies have failed and endometrial ablation is not suitable.

Universal Haplotype-Based Noninvasive Prenatal Testing for Single Gene Diseases.

BACKGROUND: Researchers have developed approaches for the noninvasive prenatal testing of single gene diseases. One approach that allows for the noninvasive assessment of both maternally and paternally inherited mutations involves the analysis of single nucleotide polymorphisms (SNPs) in maternal plasma DNA with reference to parental haplotype information. In the past, parental haplotypes were resolved by complex experimental methods or inferential approaches, such as through the analysis of DNA from other affected family members. Recently, microfluidics-based linked-read sequencing technology has become available and allows the direct haplotype phasing of the whole genome rapidly. We explored the feasibility of applying this direct haplotyping technology in noninvasive prenatal testing. METHODS: We first resolved the haplotypes of parental genomes with the use of linked-read sequencing technology. Then, we identified SNPs within and flanking the genes of interest in maternal plasma DNA by targeted sequencing. Finally, we applied relative haplotype dosage analysis to deduce the mutation inheritance status of the fetus. RESULTS: Haplotype phasing and relative haplotype dosage analysis of 12 out of 13 families were successfully achieved. The mutational status of these 12 fetuses was correctly classified. CONCLUSIONS: High-throughput linked-read sequencing followed by maternal plasma-based relative haplotype dosage analysis represents a streamlined approach for noninvasive prenatal testing of inherited single gene diseases. The approach bypasses the need for mutation-specific assays and is not dependent on the availability of DNA from other affected family members. Thus, the approach is universally applicable to pregnancies at risk for the inheritance of a single gene disease.

Direct Oral Anticoagulants and Women.

Direct oral anticoagulants (DOACs) provide an effective, safe, and convenient therapeutic alternative to warfarin and other vitamin K antagonists (VKAs), and are now established for a wide range of indications. The use of DOACs in women merits special consideration due to two main situations: first, in relation to fertility, pregnancy, and lactation in women of reproductive age; second, because of their bleeding risk, leading to abnormal uterine and/or other genital tract bleeding. This review focuses on these two clinical situations, including approaches to management in the context of available information.

Changes in thromboelastography parameters in pregnancy, labor, and the immediate postpartum period.

OBJECTIVE: To demonstrate changes in clot mechanics during pregnancy, and to determine the effect that delivery has on immediate postpartum thromboelastography parameters. METHODS: In an observational cross-sectional/longitudinal study, thromboelastography was performed on whole blood aliquots obtained from women carrying singleton pregnancies attending a center in London, UK, between December 2013 and March 2014. Thromboelastography was repeated 6hours after delivery among patients recruited in the third trimester or labor. Bleeding questionnaires were completed and routine clinical/demographic data obtained. RESULTS: Overall, 112 women were included. The thromboelastography parameters were significantly correlated with length of pregnancy. From the third trimester to the postpartum period, there was a significant decrease in time until fibrin formation (R value; 5.8 vs 5.0minutes, P=0.036) and in time to reach a certain clot strength (amplitude of 20mm; K value; 1.3 vs 1.1minutes, P=0.007). From established labor to after delivery, there was a significant increase in clot lysis at 60minutes after the maximum amplitude of clot formation (LY60; 1.8% vs 3.1%, P=0.001). CONCLUSION: The present study describes a novel finding regarding changes in clot mechanics in late pregnancy/puerperium and supports the concept of using thromboelastography as part of the routine assessments at delivery.

Plasma factor XIII level variations during menstrual cycle.

Factor XIII (FXIII) has an important role in the control of bleeding through fibrin cross-linking; however, its effect within the menstrual cycle is not fully understood. The aim of this study was to examine changes in FXIII activity during the normal menstrual cycle and correlate FXIII activity with menstrual blood loss. A total of 32 healthy normal women of reproductive age were recruited. Menstrual blood loss was measured using the pictorial blood-assessment chart (PBAC). A bleeding score questionnaire was also completed. Blood samples were taken during the menstrual, proliferative, periovulatory, secretory and premenstrual phase for assessment of FXIII level. The mean ±â€ŠSD FXIII level was lowest during menstrual and periovulatory phases (114 ±â€Š23 and 114 ±â€Š21 IU/dl, respectively). Mean FXIII level during the secretory and premenstrual phases were higher than the menstrual phase (P = 0.036). Mean secretory phase FXIII was also significantly higher compared with the periovulatory phase (P = 0.02). There was no significant correlation between FXIII level during the menstrual phase and age (P = 0.53) or PBAC score (P = 0.53). There were no significant differences in FXIII level during the menstrual phase between women with PBAC scores of at least 100 (n = 14; mean 116 IU/dl) and women with PBAC scores less than 100 (n = 18; mean 113 IU/dl). There was no correlation between FXIII level and bleeding score. FXIII activity was lower during menstrual and periovulatory phases of the cycle. However, the small difference between mean values (8 IU/dl) would be unlikely to have a significant impact on diagnosis of FXIII deficiency and clinical management.

Congenital factor V and VIII deficiency in women: a systematic review of literature and report of two new cases.

Factor V and factor VIII deficiency (F5F8D) is a rare congenital bleeding disorder. There is a paucity of data in the literature about obstetric and gynaecological problems in women affected by F5F8D. The aim of this review was to examine obstetric complications and gynaecological problems in women with congenital F5F8D and present two new cases. An electronic search was performed to identify the published literature on PUBMED, MEDLINE and EMBASE databases using the following keywords 'congenital factor V and factor VIII deficiency' and 'women or pregnancy'. A total of 23 relevant articles were found and included in this systematic review: 15 case reports and 10 case series dating from 1976 to 2015. A total number of 86 women were identified. Heavy menstrual bleeding was the most common bleeding symptom in women (49%). Recurrent ovulation bleeding and haemorrhagic ovarian cyst were reported in three women. Nineteen pregnancies were reported (including our two case reports). There were no miscarriages. Postpartum bleeding occurred in six (32%) deliveries. In conclusion, data are very limited on gynaecological and obstetric problems in women with F5F8D. Heavy menstrual bleeding is a common problem. There is also an increased risk of postpartum haemorrhage. Close collaboration between haemophilia, obstetric and gynaecological teams is important to prevent and manage obstetric and gynaecological bleeding complications.

Thrombin generation assay identifies individual variability in responses to low molecular weight heparin in pregnancy: implications for anticoagulant monitoring.

Low molecular weight heparin (LMWH) given to inhibit coagulation and reduce the risk of thrombosis, is typically monitored by anti-Xa assay. However, anti-Xa levels may not necessarily provide an accurate measure of coagulation inhibition. Moreover, pregnancy is associated with hypercoagulability, which may compromise the efficacy of LMWH. We looked at the association between anti-Xa levels and parameters of thrombin generation assay [TGA; area under the curve (AUC), peak height (PH) and time to peak (ttP)] using samples from 41 pregnant women receiving LMWH and 40 normal pregnant women controls. TGA results confirmed the physiological hypercoagulability of normal pregnancy (mean normalised values: AUC 119%; PH 157%; ttP 72%). Although anti-Xa measures correlated with all three TGA parameters, this group correlation masked significant inter-individual variability, demonstrated by the R(2) value or coefficient of determination. Anti-Xa levels contributed to 74% of variation in AUC values, 63% of variation in PH values and only 53% of variation in ttP values. The remainder reflects the contribution of patients' intrinsic coagulation status. Hence, some patients with 'safe' anti-Xa levels may potentially be under-anticoagulated, particularly in pregnancy. Measuring coagulability directly with TGA may lower the risk of adverse events due to under-anticoagulation in selected patients.

May-Hegglin anomaly and pregnancy: a systematic review.

May-Hegglin anomaly (MHA) is an autosomal dominant disorder, characterized by a variable degree of thrombocytopaenia, large platelets and inclusion bodies in white blood cells. Bleeding manifestations are generally mild, but severe bleeding episodes have been reported. This is a systematic review of literature for MHA during pregnancy. The review revealed 26 articles (25 case reports and one case series) including 75 pregnancies (five twin pregnancies) in 40 women. In 11 women, first presentation was incidental thrombocytopaenia during routine antenatal blood test. Of these, five women were misdiagnosed as idiopathic thrombocytopenic purpura (ITP), including three who underwent splenectomy for resistant ITP. Postpartum haemorrhage (PPH) and bleeding after miscarriage were presenting symptoms in two women. Antiplatelet antibody was found in three pregnancies. Only one of them required intervention with intravenous immunoglobulin (IVIG) to prevent neonatal alloimmune thrombocytopaenia. PPH was reported in four pregnancies; three were primary PPH, of which one had blood transfusion, one had platelet and cryoprecipitate transfusion and the third was managed conservatively. There was one secondary PPH that was treated conservatively. Neonatal outcome included 78 live neonates and two intrauterine fetal deaths. Thirty-four neonates had thrombocytopaenia and subsequently were diagnosed with MHA, three of them required platelet transfusion prophylactically as they developed very low platelet counts and one neonate with platelet count of 29 × 10 cells/l and received IVIG, as the mother had a positive antiplatelet antibody during pregnancy. No obvious bleeding complications were reported among the neonates. MHA can present challenges during pregnancy and be associated with adverse maternal and neonatal outcome because of bleeding complications. Joint management by obstetrician and haematologists is required to minimize these risks.

Endometrial haemostasis and menstruation.

Under normal physiological circumstances menstruation is a highly regulated, complex process that is under strict hormonal control. During normal menstruation, progesterone withdrawal initiates menstruation. The cessation of menstrual bleeding is achieved by endometrial haemostasis via platelet aggregation, fibrin deposition and thrombus formation. Local endocrine, immunological and haemostatic factors interact at a molecular level to control endometrial haemostasis. Tissue factor and thrombin play a key role locally in the cessation of menstrual bleeding through instigation of the coagulation factors. On the other hand, fibrinolysis prevents clot organisation within the uterine cavity while plasminogen activator inhibitors (PAI) and thrombin-activatable fibrinolysis inhibitors control plasminogen activators and plasmin activity. Abnormalities of uterine bleeding can result from imbalance of the haemostatic factors. The most common abnormality of uterine bleeding is heavy menstrual bleeding (HMB). Modern research has shown that an undiagnosed bleeding disorder, in particular von Willebrand disease (VWD) and platelet function disorders, can be an underlying cause of HMB. This has led to a change in the approach to the management of HMB. While full haemostatic assessment is not required for all women presenting with HMB, menstrual score and bleeding score can help to discriminate women who are more likely to have a bleeding disorder and benefit from laboratory haemostatic evaluation. Haemostatic agents (tranexamic acid and DDAVP) enhance systemic and endometrial haemostasis and are effective in reducing menstrual blood loss in women with or without bleeding disorders. Further research is required to enhance our understanding of the complex interactions of haemostatic factors in general, and specifically within the endometrium. This will lead to the development of more targeted interventions for the management of abnormal uterine bleeding in the future.

Inherited bleeding disorders in older women.

Inherited bleeding disorders (IBDs) are by definition life-long. The commonest IBD is von Willebrand disease (VWD), a deficiency of von Willebrand factor (VWF), with a prevalence 1% in the general population and 13% in women with menorrhagia. Other IBDs include carriers of haemophilia A (factor VIII deficiency) and haemophilia B, (factor IX deficiency) and rare bleeding disorders (RBDs), deficiencies of factors XI, X, V, VII, II, I and inherited platelet disorders. Diagnosis is the synthesis of a bleeding history, family history and specialised laboratory tests. Women with IBDs are more likely to suffer HMB, to be symptomatic, and to present with bleeding in association with gynaecological problems. Heavy and/or abnormal menstrual bleeding increases with age due increased anovulatory cycles and gynaecological pathologies in older women. Thus, older women with IBDs are more likely to present with gynaecological bleeding symptoms, have impaired QOL and require surgical interventions. Treatment with specific clotting factor concentrates may be required and this requires an expert in haematology. Awareness of IBDs among health care providers, early diagnosis and appropriate management in a multidisciplinary approach is required to minimise the bleeding complications for women with IBDs.

Inherited bleeding disorders in pregnancy.

Women with inherited bleeding disorders may face several haemostatic challenges during pregnancy and childbirth. Pregnancy in these women requires specialised and individualised care. Prenatal diagnosis is primarily considered in families affected by severe bleeding disorder such as haemophilia. Non-invasive fetal sex determination by analysis of free fetal DNA in maternal blood offers carriers of haemophilia a means of avoiding invasive testing and its associated risks in female pregnancies. With the exception of fibrinogen and factor XIII deficiencies, it is currently unclear whether women with inherited bleeding disorders are at increased risk of miscarriage or antepartum haemorrhage. However, they are at increased risk of primary and secondary postpartum haemorrhage. The fetus, if severely affected, is at risk of cranial bleeding during labour and delivery. Appropriate haemostatic cover during labour and delivery, avoidance of prolonged labour and traumatic delivery, and active management of third stage of labour can minimise the risk of bleeding complications for the mother and her fetus.

Thrombocytopenia and disorders of platelet function in pregnancy.

Pregnancy is associated with physiological and pathological changes in platelet numbers and function, which can be of clinical concern because of risks for maternal and fetal or neonatal bleeding. Thrombocytopenia in pregnancy is frequently encountered and may be due to increased platelet turnover and plasma dilution, immune-mediated mechanisms, or a complication of a more severe underlying pregnancy-related disorder such as preeclampsia. Inherited defects in platelet function and number may also manifest during pregnancy with the risk of bleeding dependent on the underlying problem. In some women, the diagnosis of thrombocytopenia will precede pregnancy but in others, the problem is first identified when routine pregnancy blood tests are performed. An accurate diagnosis and risk assessment in the antenatal period are essential for developing specific plans for any antenatal interventions and for management of delivery and the postpartum periods, and the neonate. Management of pregnant women with platelet disorders requires a multidisciplinary approach and close collaboration between the obstetric and hematology teams.