Inherited Bleeding Disorders in Women

Rezan A. Kadir, Paula D. James, Christine A. Lee, Rezan A. Kadir, Paula D. James, Christine A. Lee

• Editore: Wiley-Blackwell
• Anno: 2018
• ISBN:
  9781119426066
• Edizione: 2
• Argomento: Medizin
• Categoria: Hämatologie

The essential guide for understanding and treating women with inherited bleeding disorders, revised and updated

Now in its second edition, Inherited Bleeding Disorders in Women includes the most recent developments and research in the field. This important guide offers the most current information available for the effective management of these complex and difficult to diagnose disorders. Treating women with inherited bleeding disorders can be challenging and requires close collaboration among practitioners in different specialties.

This important guide is written by a team of international experts who offer advice and practical suggestions for treating women with inherited bleeding disorders. Inherited Bleeding Disorders in Women comprehensively covers obstetric and gynecological issues for carriers of hemophilia, women with von Willebrand disease, rare bleeding disorders and inherited platelet disorders. This important resource:

• Offers an updated guide for hematologists, obstetricans and gynecologists and other clinicians treating women with inherited bleeding disorders
• Includes information for treating both common and rare bleeding disorders
• Contains the most recent developments and advances in the field for the treatment and management of inherited bleeding disorders in women
• Presents information from noted experts in the field
• Offers a multidisciplinary approach to the topic

Written for hematologists, obstetricians and gynecologists and other clinicians working with women, Inherited Bleeding Disorders in Women has been fully revised and updated and continues to serve as a trusted guide for the management and treatment of women with inherited bleeding disorders.

1
Hematological Assessment of a Patient with an Inherited Bleeding Disorder

Sue Pavord and Henna Wong

Oxford University Hospitals NHS Foundation Trust, Oxford, UK

1.1 Introduction

The inherited bleeding disorders (IBDs) are a heterogeneous group of disorders affecting the hemostatic system. In individuals in whom the underlying abnormality has been identified, the majority of IBDs are due to von Willebrand disease (VWD) and disorders of coagulation factors; a small proportion are due to abnormalities in platelet count or function or defects in the fibrinolytic system [1]. Around 2% of patients registered with a bleeding disorder do not have a classifiable disorder [1].

Individuals with IBDs may give a life‐long history of excessive bruising or bleeding, but many only manifest when faced with a hemostatic challenge or are picked up incidentally by abnormal coagulation tests. Indeed some, such as certain cases of factor XI (FXI) deficiency, may not have a bleeding phenotype at all, even when exposed to hemostatic challenges. IBDs can affect all genders, but women with IBDs face added challenges related to menstruation, pregnancy, and childbirth. Undiagnosed bleeding disorders can often be the cause of heavy menstrual bleeding and also the cause of or a contributory factor for other gynecological problems, such as bleeding from the corpus luteum [2].

Women with IBDs may present with a positive bleeding history or have a known family history. Manifestations of bleeding can vary, even within the same type of disorder, because of the influence of concomitant inherited and acquired factors. An integrated clinical and laboratory assessment is therefore essential in the diagnostic work‐up.

This chapter will cover the mechanisms of normal hemostasis and an approach to the clinical and laboratory hematological assessment of a patient with a suspected IBD.

1.2 Normal Hemostasis

After damage to the lining of the blood vessel wall, the body responds with physiological mechanisms to stop bleeding and maintain hemostasis, without causing more widespread thrombosis. This co‐ordinated process involves components of the blood, including platelets and clotting factors, with the overall aim of forming a stable blood clot (Figure 1.1). Hemostasis is achieved through a delicate balance of pro‐ and anticoagulant factors to stop bleeding while simultaneously avoiding development of pathological thrombi [3].

Figure 1.1 Overview of hemostasis and key components. A vascular injury exposes collagen that allows platelets to adhere via VWF to the subendothelium. Activation of platelets occurs and platelets aggregate together via VWF and fibrinogen. Primary hemostasis results in the formation of the initial platelet plug. Tissue factor activates the coagulation pathway in parallel with platelet activation; both pathways enhance each other. Fibrinolysis prevents excessive thrombus formation, through the generation of plasmin followed by the digestion of fibrin.

Source: Modified from www.thrombocyte.com/hemostasis‐definition.

1.2.1 Primary Hemostasis

In the early stages after vessel injury, interactions between platelets, the subendothelium, and adhesive proteins lead to the formation of a platelet plug (primary hemostasis). The three main steps of primary hemostasis are as follows.

1. Platelet adhesion: following vessel injury, von Willebrand factor (VWF) binds to specific sites on exposed collagen. Platelets adhere to the exposed subendothelial matrix (directly or indirectly via VWF). This is mediated through binding of VWF with the platelet glycoprotein GP1b, while GPVI interacts with collagen, and platelet β1 integrin with laminin, collagen, and fibronectin. These interactions enable firm adhesion of platelets to the exposed subendothelial matrix [3].
2. Platelet activation: platelet adhesion to the subendothelium triggers shape change and release of platelet α and dense granule contents. This activation recruits and activates additional platelets to the injured site. (Thrombin, produced by the coagulation pathway, adds to the activation of platelets.)
3. Platelet aggregation and platelet plug formation: thrombin cleaves fibrinogen and the resulting fibrin monomers form a bridge between activated platelets, causing platelets to aggregate together, forming a platelet plug. The GPIIb/IIIa platelet receptor is converted into its high‐affinity conformation, allowing for stable interactions between the receptor and fibrin, VWF, and fibronectin.

1.2.2 Secondary Hemostasis

Secondary hemostasis usually occurs simultaneously with primary hemostasis. After endothelial damage, tissue factor (TF) is exposed, which binds to and activates FVII. The TF‐FVIIa complex then stimulates generation of small amounts of thrombin and FXIa through the extrinsic pathway. Thrombin generation is amplified through the intrinsic pathway starting with FXI and through the downstream cascade including co‐factors FVIII and FV (Figure 1.2). These enzymatic reactions occur on the surface of platelets and other cell surfaces. This leads to the formation of FXa on the platelet surface which, aided by its co‐factor, FVa, generates an explosive burst of thrombin. Thrombin catalyze...