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Inherited Bleeding Disorders in Women
Previous chapters of this book have shown the impact of bleeding disorders on women. Many women s... more Previous chapters of this book have shown the impact of bleeding disorders on women. Many women suffer a reduced quality of life [1] due to the symptoms of bleeding disorders as well as adverse medical events such as postpartum hemorrhage or prolonged bleeding ...
In 1926 von Willebrand described a bleeder family in Aland; this condition became known as von Wi... more In 1926 von Willebrand described a bleeder family in Aland; this condition became known as von Willebrand disease (VWD). von Willebrand noted that "the trait seemed especially to be seen among the women." Today, the use of a pictorial bleeding assessment chart (PBAC) has enabled the prevalence of VWD to be established among women presenting with menorrhagia, as well as the documentation of this symptom in women with known VWD and the assessment of treatment response in menorrhagia. Treatments for menorrhagia include tranexamic acid, desmopressin (DDAVP) administered either intranasally or subcutaneously, the oral contraceptive pill, the "Mirena" coil (Schering Oy, Turku, Finland), and endometrial ablation. Von Willebrand factor (VWF) shows strong cyclical variation, with peak values occurring in the luteal phase. Although increased in pregnancy, levels of VWF decline postnatally and the incidence of both primary and secondary postpartum hemorrhage is high (20% to 25%). Baseline VWF levels less than 15 IU/dL are unlikely to reach greater than 50 IU/dL in the third trimester, and therefore prophylaxis with DDAVP or VWF-containing concentrate to cover delivery should be considered. Semin Hematol 42:42-48
BMJ case reports, 2010
Two patients with recent H1N1 virus infection in pregnancy were found to have raised transaminase... more Two patients with recent H1N1 virus infection in pregnancy were found to have raised transaminases. They have both had a mild illness and have recovered with no adverse effects, and one has delivered a healthy baby while the other is still pregnant. We suggest that the deranged transaminase concentrations were directly linked to the viral infection in the first patient as the abnormal blood results predated treatment. The second case is less clear.
Transfusion, 2014
Postpartum hemorrhage (PPH) remains one of the leading causes of maternal morbidity and mortality... more Postpartum hemorrhage (PPH) remains one of the leading causes of maternal morbidity and mortality worldwide, although the lack of a precise definition precludes accurate data of the absolute prevalence of PPH. An international expert panel in obstetrics, gynecology, hematology, transfusion, and anesthesiology undertook a comprehensive review of the literature. At a meeting in November 2011, the panel agreed on a definition of severe PPH that would identify those women who were at a high risk of adverse clinical outcomes. The panel agreed on the following definition for severe persistent (ongoing) PPH: "Active bleeding >1000 mL within the 24 hours following birth that continues despite the use of initial measures including first-line uterotonic agents and uterine massage." A treatment algorithm for severe persistent PPH was subsequently developed. Initial evaluations include measurement of blood loss and clinical assessments of PPH severity. Coagulation screens should be performed as soon as persistent (ongoing) PPH is diagnosed, to guide subsequent therapy. If initial measures fail to stop bleeding and uterine atony persists, second- and third-line (if required) interventions should be instated. These include mechanical or surgical maneuvers, i.e., intrauterine balloon tamponade or hemostatic brace sutures with hysterectomy as the final surgical option for uncontrollable PPH. Pharmacologic options include hemostatic agents (tranexamic acid), with timely transfusion of blood and plasma products playing an important role in persistent and severe PPH. Early, aggressive, and coordinated intervention by health care professionals is critical in minimizing blood loss to ensure optimal clinical outcomes in management of women with severe, persistent PPH.
Thrombosis and Haemostasis, 2011
Although factor XI (FXI) concentrate is an effective replacement therapy in severe FXI deficiency... more Although factor XI (FXI) concentrate is an effective replacement therapy in severe FXI deficiency without inhibitors, some patients are unwilling to receive it because it is plasma-derived. We report on the use and monitoring of low dose, recombinant factor VIIa (rFVIIa, NovoSeven®), to cover surgery (caesarean section, cholecystectomy and abdominoplasty) in four female patients (FXI:C 2-4 IU/dl, aged 32-51 years) who wished to avoid exposure to plasma. None of our patients had inhibitors to FXI. Our aim was to find the optimal dose of rFVIIa by in vitro spiking of patient samples and to correlate this with the response to rFVIIa in vivo . Prior to surgery, venous blood was collected into sodium citrate with corn trypsin inhibitor and spiked with 0.25-1.0 μg/ml rFVIIa in vitro , equivalent to a 15-70 μg/kg dose of rFVIIa in vivo . Analysis using thromboelastometry and thrombin generation assays, triggered with tissue factor, showed that the thrombin generation assay was insufficiently sensitive to the haemostatic defect in these patients. A concentration of 0.5 μg/ml was as effective as 1.0 μg/ml FVIIa in normalising thromboelastometry in vitro in all four patients. Therefore, patients received 15-30 μg/kg rFVIIa at 2-4 hourly intervals with tranexamic acid 1g every six hours. Post treatment samples were taken at 10-240 minutes and showed initial normalisation of thromboelastometry with gradual return to baseline after 2-4 hours. In conclusion, low-dose rFVIIa therapy was successfully used in four patients with severe FXI deficiency undergoing surgery to prevent bleeding and can be monitored using thromboelastometry.
European Journal of Obstetrics & Gynecology and Reproductive Biology, 2011
Acute menorrhagia is a common gynecological disorder. Prevalence is high among women with inherit... more Acute menorrhagia is a common gynecological disorder. Prevalence is high among women with inherited bleeding disorders and recent guidance for optimal management is lacking. Following a comprehensive review of the literature, an international expert panel in obstetrics, gynecology and hematology reached consensus on recommendations regarding the management of acute menorrhagia in women without a diagnosed bleeding disorder, as well as in patients with von Willebrand disease, platelet function disorders and other rare hemostatic disorders. The causes and predictors of acute menorrhagia are discussed and special consideration is given for the treatment of women on anticoagulation therapy. This review and accompanying recommendations will provide guidance for healthcare practitioners in the emergency management of acute menorrhagia.
Acta Obstetricia et Gynecologica Scandinavica, 2005
... A diagnostic dilemma: round ligament varicosities in pregnancy. Claudia Chi,; Alex Taylor,; N... more ... A diagnostic dilemma: round ligament varicosities in pregnancy. Claudia Chi,; Alex Taylor,; Nalini Munjuluri,; Rezan Abdul-Kadir. Article first published online: 17 OCT 2005. DOI: 10.1111/j.0001-6349.2005.00120c.x. Issue. Acta Obstetricia et Gynecologica Scandinavica. ...
American Journal of Obstetrics and Gynecology, 2009
Inherited Bleeding Disorders in Women
Previous chapters of this book have shown the impact of bleeding disorders on women. Many women s... more Previous chapters of this book have shown the impact of bleeding disorders on women. Many women suffer a reduced quality of life [1] due to the symptoms of bleeding disorders as well as adverse medical events such as postpartum hemorrhage or prolonged bleeding ...
In 1926 von Willebrand described a bleeder family in Aland; this condition became known as von Wi... more In 1926 von Willebrand described a bleeder family in Aland; this condition became known as von Willebrand disease (VWD). von Willebrand noted that "the trait seemed especially to be seen among the women." Today, the use of a pictorial bleeding assessment chart (PBAC) has enabled the prevalence of VWD to be established among women presenting with menorrhagia, as well as the documentation of this symptom in women with known VWD and the assessment of treatment response in menorrhagia. Treatments for menorrhagia include tranexamic acid, desmopressin (DDAVP) administered either intranasally or subcutaneously, the oral contraceptive pill, the "Mirena" coil (Schering Oy, Turku, Finland), and endometrial ablation. Von Willebrand factor (VWF) shows strong cyclical variation, with peak values occurring in the luteal phase. Although increased in pregnancy, levels of VWF decline postnatally and the incidence of both primary and secondary postpartum hemorrhage is high (20% to 25%). Baseline VWF levels less than 15 IU/dL are unlikely to reach greater than 50 IU/dL in the third trimester, and therefore prophylaxis with DDAVP or VWF-containing concentrate to cover delivery should be considered. Semin Hematol 42:42-48
BMJ case reports, 2010
Two patients with recent H1N1 virus infection in pregnancy were found to have raised transaminase... more Two patients with recent H1N1 virus infection in pregnancy were found to have raised transaminases. They have both had a mild illness and have recovered with no adverse effects, and one has delivered a healthy baby while the other is still pregnant. We suggest that the deranged transaminase concentrations were directly linked to the viral infection in the first patient as the abnormal blood results predated treatment. The second case is less clear.
Transfusion, 2014
Postpartum hemorrhage (PPH) remains one of the leading causes of maternal morbidity and mortality... more Postpartum hemorrhage (PPH) remains one of the leading causes of maternal morbidity and mortality worldwide, although the lack of a precise definition precludes accurate data of the absolute prevalence of PPH. An international expert panel in obstetrics, gynecology, hematology, transfusion, and anesthesiology undertook a comprehensive review of the literature. At a meeting in November 2011, the panel agreed on a definition of severe PPH that would identify those women who were at a high risk of adverse clinical outcomes. The panel agreed on the following definition for severe persistent (ongoing) PPH: "Active bleeding >1000 mL within the 24 hours following birth that continues despite the use of initial measures including first-line uterotonic agents and uterine massage." A treatment algorithm for severe persistent PPH was subsequently developed. Initial evaluations include measurement of blood loss and clinical assessments of PPH severity. Coagulation screens should be performed as soon as persistent (ongoing) PPH is diagnosed, to guide subsequent therapy. If initial measures fail to stop bleeding and uterine atony persists, second- and third-line (if required) interventions should be instated. These include mechanical or surgical maneuvers, i.e., intrauterine balloon tamponade or hemostatic brace sutures with hysterectomy as the final surgical option for uncontrollable PPH. Pharmacologic options include hemostatic agents (tranexamic acid), with timely transfusion of blood and plasma products playing an important role in persistent and severe PPH. Early, aggressive, and coordinated intervention by health care professionals is critical in minimizing blood loss to ensure optimal clinical outcomes in management of women with severe, persistent PPH.
Thrombosis and Haemostasis, 2011
Although factor XI (FXI) concentrate is an effective replacement therapy in severe FXI deficiency... more Although factor XI (FXI) concentrate is an effective replacement therapy in severe FXI deficiency without inhibitors, some patients are unwilling to receive it because it is plasma-derived. We report on the use and monitoring of low dose, recombinant factor VIIa (rFVIIa, NovoSeven®), to cover surgery (caesarean section, cholecystectomy and abdominoplasty) in four female patients (FXI:C 2-4 IU/dl, aged 32-51 years) who wished to avoid exposure to plasma. None of our patients had inhibitors to FXI. Our aim was to find the optimal dose of rFVIIa by in vitro spiking of patient samples and to correlate this with the response to rFVIIa in vivo . Prior to surgery, venous blood was collected into sodium citrate with corn trypsin inhibitor and spiked with 0.25-1.0 μg/ml rFVIIa in vitro , equivalent to a 15-70 μg/kg dose of rFVIIa in vivo . Analysis using thromboelastometry and thrombin generation assays, triggered with tissue factor, showed that the thrombin generation assay was insufficiently sensitive to the haemostatic defect in these patients. A concentration of 0.5 μg/ml was as effective as 1.0 μg/ml FVIIa in normalising thromboelastometry in vitro in all four patients. Therefore, patients received 15-30 μg/kg rFVIIa at 2-4 hourly intervals with tranexamic acid 1g every six hours. Post treatment samples were taken at 10-240 minutes and showed initial normalisation of thromboelastometry with gradual return to baseline after 2-4 hours. In conclusion, low-dose rFVIIa therapy was successfully used in four patients with severe FXI deficiency undergoing surgery to prevent bleeding and can be monitored using thromboelastometry.
European Journal of Obstetrics & Gynecology and Reproductive Biology, 2011
Acute menorrhagia is a common gynecological disorder. Prevalence is high among women with inherit... more Acute menorrhagia is a common gynecological disorder. Prevalence is high among women with inherited bleeding disorders and recent guidance for optimal management is lacking. Following a comprehensive review of the literature, an international expert panel in obstetrics, gynecology and hematology reached consensus on recommendations regarding the management of acute menorrhagia in women without a diagnosed bleeding disorder, as well as in patients with von Willebrand disease, platelet function disorders and other rare hemostatic disorders. The causes and predictors of acute menorrhagia are discussed and special consideration is given for the treatment of women on anticoagulation therapy. This review and accompanying recommendations will provide guidance for healthcare practitioners in the emergency management of acute menorrhagia.
Acta Obstetricia et Gynecologica Scandinavica, 2005
... A diagnostic dilemma: round ligament varicosities in pregnancy. Claudia Chi,; Alex Taylor,; N... more ... A diagnostic dilemma: round ligament varicosities in pregnancy. Claudia Chi,; Alex Taylor,; Nalini Munjuluri,; Rezan Abdul-Kadir. Article first published online: 17 OCT 2005. DOI: 10.1111/j.0001-6349.2005.00120c.x. Issue. Acta Obstetricia et Gynecologica Scandinavica. ...
American Journal of Obstetrics and Gynecology, 2009