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Hypercoagulable States

Arterial and venous thromboses are common problems for all clinicians. Some patients with thrombosis have an underlying hypercoagulable state. These hypercoagulable states can be divided into three categories: inherited disorders, acquired disorders, and those that are mixed in origin. Inherited hypercoagulable states, also known as thrombophilic disorders, can be due to loss of function of natural anticoagulant pathways or gain of function in procoagulant pathways (…

Disseminated Intravascular Coagulation

A variety of disorders, including infectious or inflammatory conditions and malignant disease, will lead to activation of coagulation. In many cases, this activation of coagulation will not lead to clinical complications and will not even be detected by routine laboratory tests, but can only be measured with sensitive molecular markers for activation of coagulation factors and pathways. However, if activation of coagulation is sufficiently strong, the…

Transfusion Therapy for Coagulation Factor Deficiencies

This chapter reviews products available to treat deficiencies of plasma coagulation proteins. The development of blood component therapy and subsequently protein concentrates that are enriched in particular coagulation factors and other proteins made possible the effective treatment of bleeding episodes in patients with hemophilia and other diatheses. In the 1940s, a collaborative effort funded by the US government was undertaken among protein scientists with the goal…

Rare Coagulation Factor Deficiencies

The term “rare coagulation factor deficiency” refers to disorders of thrombin and/or fibrin formation caused by mutations in a single gene, other than those for von Willebrand factor (see Chapter 133 ), factor VIII, or factor IX (see Chapter 134 ), that reduce plasma activity of one or more coagulation proteins. The most common inherited deficiencies that cause defects in plasma coagulation are those for factor…

Hemophilia A and B

Hemophilia is the most common, severe inherited bleeding disorder recognized in humans. The X-linked mode of inheritance has been appreciated since biblical times, and the previous occurrence of the disease in the European royal family has added further interest in this condition. Hemophilia is subdivided into hemophilia A and B; the former being a deficiency or absence of factor (F) VIII while the latter is a…

Structure, Biology, and Genetics of von Willebrand Factor

Von Willebrand factor (VWF) is an adhesive multimeric plasma glycoprotein (GP) that mediates platelet adhesion to injured subendothelium via GPIbα, and binds and stabilizes factor VIII (FVIII) in the circulation, protecting it from proteolytic degradation. This important multifunctional protein was named after the Finnish physician Dr. Erik von Willebrand, who first described von Willebrand disease (VWD) in 1926. In the original publication, he described a severe…

Thrombotic Thrombocytopenic Purpura and the Hemolytic Uremic Syndromes

In 1924, Moschowitz reported a case of a 16-year-old girl who died of a previously undescribed illness characterized by microangiopathic hemolytic anemia (MAHA), petechiae, hemiparesis, and fever. Postmortem examination revealed numerous hyaline thrombi, most prevalent in the terminal arterioles and capillaries of the heart and kidneys. In 1936, four similar cases were reported by Baehr and colleagues, who proposed that the hyaline thrombi were secondary to…

Heparin-Induced Thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is the most important drug-induced immune-mediated cytopenia for several reasons. First, heparin is a widely used anticoagulant (see Chapter 143 ). Second, HIT is relatively common, occurring in approximately 1% to 3% of postoperative patients, and 0.2% to 0.5% of medical patients, who receive unfractionated heparin (UFH) derived from porcine intestine for 7 to 14 days. Third, HIT frequently causes life- and limb-threatening…

Thrombocytopenia Caused by Hypersplenism, Platelet Destruction, or Surgery/Hemodilution

Thrombocytopenia is defined as a platelet count below the lower limit of the normal range (≈150 × 10 9 /L). Sometimes, an expanded definition of thrombocytopenia is appropriate. For example, an abrupt drop in the platelet count can signify the onset of a disorder such as heparin-induced thrombocytopenia (HIT) or bacteremia even if the platelet count remains above 150 × 10 9 This is especially…

Diseases of Platelet Number: Immune Thrombocytopenia, Neonatal Alloimmune Thrombocytopenia, and Posttransfusion Purpura

Platelets are anucleate cells that are required for primary hemostasis. A normal platelet count is 150,000 to 400,000 platelets per microliter of blood, with a normal lifespan of 7 to 10 days for circulating platelets. The body clears 10 11 platelets per day by balancing complex proapoptotic and antiapoptotic mechanisms. Exogenous reagents and environmental changes can also impact the rate of platelet clearance by the cells…

Acquired Disorders of Platelet Function

Acquired disorders of platelet function are among the most common hematologic abnormalities, which reflects the sensitivity of platelets to external and internal perturbations. The clinical challenge in evaluating acquired disorders of platelet function is to determine whether observed derangements in platelet function pose a threat to the patient. Although altered platelet function can predispose patients to either hemostatic or thrombotic disorders, this chapter deals primarily, but…

Laboratory Evaluation of Hemostatic and Thrombotic Disorders

This chapter provides a practical approach to the laboratory evaluation of hemostatic and thrombotic disorders. Any assessment of hemostatic or thrombotic disorders must start with a thorough history and physical examination. These can provide clues to guide subsequent laboratory testing, diagnosis, and management. Physiologic hemostasis is a complex interplay of cellular or plasma elements: the adhesion of platelets to damaged endothelium, the aggregation of platelets to…

Evaluation of the Patient With Suspected Bleeding Disorders

Bruising and bleeding are common reasons for a hematology referral. Some consults are for management of an acute bleed in someone who may have a hemorrhagic disorder. Such bleeds may be spontaneous or occur after surgery or trauma, and the potential bleeding disorder may be inherited or acquired. With acute bleeding problems, the approach to patients must be rapid and directed at urgent restoration of hemostasis.…

Molecular Basis of Blood Coagulation

Blood is the principal vehicle delivering oxygen and nutrients to the various tissues and organs of the body. Blood flow and the integrity of the vasculature are essential to life itself. The hemostatic process has evolved to provide damage recognition and protection from blood loss after perforation of the vasculature while at the same time preventing the systemic activation of the clotting system. However, pathologic occlusions…

Molecular Basis of Platelet Function

A primary physiological role of platelets is to support hemostasis at sites of vascular injury by forming a plug that arrests blood loss ( Fig. 124.1 ). Normally, disc-shaped platelets circulate in the bloodstream without adhering to the endothelium of the vessel wall. When the endothelium is damaged, platelets adhere to the exposed subendothelial collagen and, at high shear, to collagen-immobilized von Willebrand factor (VWF). Platelet…

Megakaryocyte And Platelet Structure

Platelets are small anucleate fragments that are formed from the cytoplasm of megakaryocytes and have a characteristic discoid shape. To assemble and release platelets, megakaryocytes become polyploid by endomitosis and follow a maturation program that results in the conversion of the bulk of their cytoplasm into multiple long processes called proplatelets . To produce its quota of 1000 to 2000 platelets, a megakaryocyte may release as…

Blood Vessels

Hemostatic, Hematopoietic, and Vascular Systems as a Functional Continuum Diseases affecting the bone marrow (BM) and peripheral blood are closely intertwined with the state of the vascular system, which acts as a niche, conduit, and regulator of blood cells. This is exemplified by the anatomic proximity and interactions among several related cellular populations, including hematopoietic stem and progenitor cells and their mature progeny, endothelial cells, perivascular…

Overview of Hemostasis and Thrombosis

Introduction Hemostasis preserves vascular integrity by balancing the physiologic processes that maintain blood in a fluid state under normal circumstances and prevent excessive bleeding after vascular injury. Preservation of blood fluidity depends on an intact vascular endothelium, and a complex series of regulatory pathways that maintain platelets in a quiescent state and keep the coagulation system in check. In contrast, arrest of bleeding requires rapid formation…

Transfusion and Apheresis Support for Sickle Cell Disease Patients

Transfusion of red cells in all patients is primarily triggered by the need to increase oxygen delivery to tissues in the setting of blood loss or anemia. For patients with sickle cell disease (SCD), there are additional considerations for transfusion including the need to remove sickle hemoglobin (HbS) containing cells in specific clinical settings. These settings include acute complications (e.g., acute chest syndrome) of SCD or…

Pediatric Transfusion Medicine

A variety of neonatal and pediatric patients require blood component transfusions. This chapter focuses on aspects of blood-bank laboratory testing, blood products and components, transfusion indications, and potential adverse events that are specifically relevant to neonates and children. Pediatric Blood Banking Blood and Blood Components Several different blood components, including whole blood, reconstituted whole blood, red blood cells (RBCs), platelets, plasma, and cryoprecipitated antihemophilic factor (CRYO)…