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Thrombophilia in Pregnancy

Introduction Pregnancy is associated with an increased risk of venous thromboembolism (VTE). This increased risk is mediated by physiologic changes that occur during and immediately following pregnancy and that may have enhanced survival during evolution by decreasing hemorrhage at parturition. These alterations in hemostasis may favor coagulation (decreased levels of free protein S [PS] and increased levels of factor VIII and factor X, von Willebrand factor…

Bleeding and the Management of Hemorrhagic Disorders in Pregnancy

Introduction Successful management of bleeding in pregnancy requires an understanding of the various scenarios in pregnancy in which bleeding can arise. In this chapter the discussion is focused on pregnancy-related bleeding, including bleeding due to obstetric, surgical, and systemic causes. Surgical bleeding is bleeding caused by incisions, lacerations, ruptured vessels, or ruptured viscus and includes the bleeding that accompanies birth trauma, cesarean delivery, or a ruptured…

Thrombotic Risk of Contraceptives and Other Hormonal Therapies

Hormones are administered in various forms for contraception, postmenopausal symptom management, treatment of hormone-responsive cancers, breast cancer risk reduction, and therapy in transgender individuals. This chapter will focus on the association of estrogen and/or progestin therapy with thromboembolic disease. The benefits of these drugs will be discussed in less detail. In deciding whether to prescribe hormone therapy, one must assess the risk-to-benefit ratio for that individual.…

Use of Vena Cava Filters and Venous Access Devices

Vena Cava Filters Introduction Venous thromboembolism (VTE), a disease entity that includes deep venous thrombosis (DVT) and pulmonary embolism (PE), is a common cause of morbidity and mortality in the United States. Administrative data indicate that 467,000 patients in this country are hospitalized annually with a DVT and 247,000 with a PE. Most patients can be managed safely with anticoagulation, but bleeding complications or presence of…

Therapeutic Apheresis—Applications for Hemorrhagic and Thrombotic Disorders

Overview and Technical Considerations The clinical procedures collectively referred to as apheresis involve the separation of a solute or cellular component of the blood for removal or for treatment and reinfusion. Apheresis was first introduced as a novel therapeutic modality in the 1950s. By the early 1960s plasma removal (plasmapheresis) was being used to manage selected patients with monoclonal paraproteinemia due to myeloma or Waldenström macroglobinemia.…

Blood Component and Pharmacologic Therapy for Hemostatic Disorders

Synopsis Patients with disordered hemostasis present one of the greatest challenges to blood banks and transfusion practitioners. Early intervention with appropriate directed therapy can provide adequate hemostasis in a variety of bleeding conditions; however, the rapidly hemorrhaging patient can deplete the transfusion service's inventory and pose a major challenge to the hospital and the community. With the availability of alternatives to blood such as recombinant factor…

Parenteral Antithrombotic Agents

Introduction Antithrombotic agents have been in clinical use for more than half a century and are among the most commonly prescribed classes of medications. Established uses include the prevention and treatment of venous thromboembolism (VTE), atrial fibrillation (AF), and acute coronary syndromes (ACSs), and prevention of embolism from mechanical heart valves. Both oral and parenteral agents exist, each with various indications and therapeutic targets. The most…

Heparin-Induced Thrombocytopenia

Historical Overview In 1958 a vascular surgeon, Rodger Weismann, and his resident, Richard Tobin, reported on 10 patients from whom they had extracted unusual platelet-fibrin thrombi that formed during a 1- to 2-week course of treatment with heparin. These physicians suspected a causal relationship with heparin, perhaps via heparin-induced embolization of thrombus from the proximal aorta (the paucity of red cells in the thrombi argued against…

Complement-Mediated Coagulation Disorders: Paroxysmal Nocturnal Hemoglobinuria and Atypical Hemolytic Uremic Syndrome

Introduction Complement is an elaborate system that participates in the innate immune response. Mutations and autoantibodies leading to unregulated complement activation are implicated in the pathogenesis of a variety of human diseases. Among them, paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) are well-established disorders of complement dysregulation. Diseases associated with complement dysregulation are often associated with thrombosis, highlighting the close interaction between the…

Thrombotic Thrombocytopenic Purpura and Related Thrombotic Microangiopathies

Introduction Thrombotic thrombocytopenic purpura (TTP) is one of the most devastating thrombotic disorders of humans and carries a mortality rate of about 90% if untreated. Even with current state-of-the art therapy, mortality has not improved significantly over the past 3 decades, remaining at about 20% per episode. Recent breakthroughs in understanding the mechanisms of this remarkable and heterogeneous disorder lend confidence that we will be able…

Thrombosis and Cancer

Introduction Patients with cancer are highly susceptible to venous thromboembolism (VTE), as well as arterial thromboembolic events, complications that contribute significantly to the morbidity and mortality of the disease. There is an abundance of epidemiologic evidence to support the close-knit relationship between thrombosis and cancer. The risk of an episode of idiopathic VTE within 6 to 12 months of a new cancer diagnosis approaches 10%. Many…

Nonarteriosclerotic Disorders of the Arterial System

Pathophysiology of Arterial Thrombosis In general, venous thrombosis is caused by disturbances in the plasma coagulation system, with platelet participation playing a minor role, whereas in arterial thrombosis, platelets play the major role with limited participation of the plasma coagulation system. This pattern helps explain why coagulation protein abnormalities—such as the presence of factor V Leiden (FVL), the prothrombin 20210 mutation, and deficiencies of protein C,…

Antiplatelet Therapy in Cardiovascular Medicine

The evolution of cardiovascular (CV) medicine has flourished with advancements in our understanding of vascular biology, hemostasis, and thrombosis. Pharmacotherapies for the prevention and treatment of coronary atherothrombosis are the end results of several decades of investigation, highlighted by robust collaborative efforts between cardiology, pathology, and hematology communities in response disease pathologies ( Table 21.1 ). This chapter summarizes CV medicine's rapid evolution, with particular focus…

Antiphospholipid Syndrome

Introduction The first studies identifying what would eventually become known as antiphospholipid antibodies appeared in the 1950s, in patients with biologic false-positive tests for syphilis who also exhibited unusual coagulation test results consistent with the presence of a “circulating anticoagulant.” The association between the presence of these circulating anticoagulants and thromboembolic events was first noted by Bowie and colleagues in 1963. The term lupus anticoagulant (LAC)…

Thrombocytosis: Essential Thrombocythemia and Reactive Causes

Introduction Thrombocytosis is defined as a platelet count greater than 450,000/µL, which is typically considered the upper limit of the normal laboratory reference range of 150,000 to 450,000 Thrombocytosis is most frequently detected as an incidental laboratory abnormality, and subsequently a causal explanation is sought. Thrombocytosis may be pragmatically categorized as (1) nonclonal; (2) due to hereditary, reactive, or spurious causes; or (3) an autonomous clonal…

Postthrombotic Syndrome

Synopsis Postthrombotic syndrome (PTS) is the most common complication of deep vein thrombosis (DVT). After an episode of proximal DVT, 20% to 50% of patients develop PTS and 5% to 10% of patients develop severe PTS, a condition that reduces quality of life and is associated with increased costs and health resource utilization. The most important risk factors for PTS are proximal location of the DVT…

Venous Thromboses at Unusual Sites

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are the most commonly encountered examples of venous thromboembolism (VTE). Given the frequency of both DVT and PE, treatment is guided by the results of randomized clinical trials. DVT and PE are discussed thoroughly in Chapter 16 . VTE that occurs at unusual locations—for example, in the intracerebral, retinal, or intraabdominal venous circulation—is being diagnosed with increasing frequency,…

Prevention and Treatment of Venous Thromboembolism

Epidemiology Venous thromboembolism (VTE), whose principal clinical manifestations include deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common cause of morbidity and mortality. The annual incidence of VTE has been estimated to be 104 to 183 per 100,000 among whites of European enthnicity. In an analysis of the California Discharge dataset, White et al. noted that the incidence of VTE was higher among African Americans…

Pediatric Aspects of Thrombophilia

Introduction Compared with adults, children are relatively protected from venous and arterial thrombosis. Advances in the treatment and supportive care of critically ill children, along with heightened awareness of thrombotic complications, have resulted in an increase in the diagnosis of thromboembolic events. Greater recognition of genetic risk factors for thrombosis has led to controversy regarding whether children with thrombosis or a family history of thrombosis should…

Thrombophilia: Clinical and Laboratory Assessment and Management

Introduction Venous thromboembolism (VTE) poses a number of challenges and opportunities to the practicing hematologist. The duration of anticoagulation is a frequent reason for consultation because it poses difficult questions of risk and benefit. Although the practical frustrations of anticoagulation to patients have been slightly mitigated by the arrival of alternatives to warfarin, weighing the risks of bleeding compared with clotting remains as challenging as ever.…