Disorders of Coagulation

Hemophilia A and B (Christmas disease) are sex-linked recessive diseases caused by a deficiency of clotting factor VIII and IX, respectively. They are major causes of childhood intracerebral hemorrhages.

In inherited hypercoagulability, mutation of coagulation factor V gene (factor Leiden) has been associated with ischemic strokes in children. Diseases with protein-C, protein-S, and antithrombin-III deficiencies are inherited in an autosomal dominant pattern. They affect young adults and present with recurrent venous thrombosis.

Antiphospholipid antibody syndrome is an important acquired coagulation disorder in young individuals (Fig. 4.39). Antiphospholipid antibodies (aPL) are a group of circulating immunoglobulins (IgG, IgM, and

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FIGURE 4.37

Sickle cell crisis with fulminant fatal hypoxic-ischemic encephalopathy in a 20-year-old African American woman with sickle cell trait. Following strenuous physical exercises, her illness began with abdominal and joint pain, and culminated 3 days after the onset in coma and death. A. Bone marrow shows closely packed sickled erythrocytes and hemorrhages (HE). B. Petechiae are scattered throughout the white and gray matter. C. Multiple discrete lesions are dispersed in the cortex and white matter of the occipital lobe and in (D) thalamus and basal ganglia (LFB-CV). E. Within the lesions, the myelin and nerve fibers are variably destroyed (Holmes stain). F. The cortex shows focal ischemic neuronal necrosis (HE). G. Sludging and sickling of erythrocytes are noticeable in the lumen of a small vessel (HE).

IgA). Among them, the anticardiolipin antibody and the lupus anticoagulant are the best characterized. Antiphos-pholipid antibodies are present in a high percentage of patients with lupus erythematosus. The aPL antibodies predispose to intravascular thrombotic events and infarctions through a complex immune-mediated mechanism.

The syndrome is associated with widespread recurrent arterial and venous thrombosis in the brain, retina, visceral organs, and peripheral blood vessels. Charac teristic neurologic manifestations are TIAs, ischemic strokes, amaurosis fugax, migraine-like headaches, seizures, ischemic encephalopathy and, in severe cases, the disease progresses to dementia. Cardiac valvular diseases (verrucous endocarditis), cutaneous lesions (livedo reticularis), and recurrent abortions in women are common systemic manifestations. Thrombocytopenia, prolonged activated thromboplastin time and prothrom-bin time, and high titers of antiphospholipid antibodies are laboratory hallmarks of the syndrome.

FIGURE 4.38

Complications of hematologic diseases. A. Polycythemia vera in a 67-year-old man. MRI shows a pontine lacunar infarct. B. Acute myelocytic leukemia in a 52-year-old man complicated by temporal lobe hemorrhage. C. Thrombocytopenia in a 67-year-old alcoholic patient associated with thalamic hemorrhage. D. Thrombotic thrombocytopenic purpura. Hyalin platelet thrombus occludes the lumen of a capillary (HE).

FIGURE 4.38

Complications of hematologic diseases. A. Polycythemia vera in a 67-year-old man. MRI shows a pontine lacunar infarct. B. Acute myelocytic leukemia in a 52-year-old man complicated by temporal lobe hemorrhage. C. Thrombocytopenia in a 67-year-old alcoholic patient associated with thalamic hemorrhage. D. Thrombotic thrombocytopenic purpura. Hyalin platelet thrombus occludes the lumen of a capillary (HE).

FIGURE 4.39

Antiphospholipid antibody syndrome in a 48-year-old man. He suffered his first stroke at age 31 years and the second at age 33. T2-weighted MRI shows multiple infarcts in territories of MCAs. Recurrent TIAs, slowly progressive neurologic deficits, dysarthria, and memory decline define his clinical course.

Antiphospholipid antibodies have been associated with malignancies, Lyme disease, HIV infection, and benign intracranial hypertension. They occasionally occur in patients treated with Dilantin, valproic acid, and phenothiazine drugs. In all these conditions, they seldom produce the syndrome.

Disseminated intravascular coagulation (DIC), a thrombohemorrhagic disorder, is associated with a variety of diseases, including infection, liver disease, neoplasm, trauma, burns, and obstetric complications. Fibrin thrombi in the small arteries and capillaries of the brain, viscera, and skin cause microinfarcts and microhemorrhages. Hemorrhages are more common in acute disease, whereas infarcts are more common in chronic disease.

Cerebral sinovenous thrombosis may develop in a variety of clinical settings, including liver disease, nephrotic syndrome, fracture, burns, malignancy, pregnancy, postpartum and postoperative states, the use of birth control pills, and dehydration. It can cause sub-arachnoid and intracerebral hemorrhages and bland or hemorrhagic infarcts. The lesions are commonly situated in the cortex and subcortical white matter (Fig. 4.40).

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