Introduction

Hematological diseases are uncommon causes of strokes resulting in approximately 10% of strokes
in young patients and 19 of all patients with ischemic stroke.

Hyperviscosity
Sickle cell anemia contributes to hyperviscosity leading to large arterial, watershed
infarcts. Intracerebral hemorrhage has also been reported. Intracerebral arteriopathy can be
monitored with non-invasive imaging such as transcranial Doppler ultrasound and magnetic
resonance imaging Blood transfusion has been shown in randomized clinical trials to reduce stroke
risk bul has to be administered on a long-term b Children become vulnerable for recurrence of
stroke if blood transfusion is suspended Hydroxyurea, antiplatelet, other antithrombotic agents and
bone marrow transplantation are possible treatment options but remain to be tested in valid clinical
trials to confirm their efficacy in stroke prevention outside Africa, sickle cell anemia is most
prevalent in North America, with 83% of African Americans carrying the sickle trail and 0.16%
the disease. Sickle cell anemia is increasingly noticed in Europe because of immigration but is
relatively uncommon in Asia except for the Middle East.

Prothrombotic disorders
Prothrombolic coagulation abnormalities are complex and rapidly evolving. Inherited
thrombophilias including deficiency in antithrombin (AT, protein C and protein S predispose
carriers to cerebral venous thrombosis, peripheral venous thrombosis and, rarely, arterial
thrombosis, including stroke. AT is an inhibitor of thrombin and other activated clotting factors.
Deficiency in AT has a prevalence of 1 in 250 500 in the general population. It is inherited in an
autosomal dominant pattern. The prevalence of hereditary AT deficiency is 0.5-1% among patients
after a first thrombotic event, Clinical events are usually precipitated by pregnancy, surgery,
infection, or oral contraceptives Treatment of symptomatic inherited AT deficiency is with
warfarin. AT deficiency is resistant to anticoagulation with heparin. Alternatively, replacement
AT is available for short-term therapy or during episodes of high risk.
Protein C is an important inhibitor of plasma coagulation. is activated when clotting is
initiated on the endothelial surface. Protein 5 acts as a non-Enzymatic cofactor for the activated
protein C (APCI, APC and protein S collectively confer anticoagulant actions and also activate
fibrinolysis. Most affected adult patients are heterozygous for Protein C deficiency with prevalence
1 in 200 50m in the general population. The prevalence of protein S deficiency is estimated at 1 in
700-3000
Both conditions are inherited in an autosomal dominant pattern with partial expressivity.
Premature stroke also affects children and young adults heterozygous for protein C deficiency
when conventional stroke risk factors are also present. Acquired protein C deficiency may occur
with liver disease, vitamin K malabsorption, infection, sepsis, disseminated intravascular
coagulation, or malignancy Homocystinuria (see below) in association with protein C deficiency
has been recognized to cause thrombotic episodes. Acquired protein S deficiencies can also occur
with nephrotic syndrome, HIV infection, and L-asparaginase chemotherapy in addition to oral
contraceptive use and liver dysfunction.
Activated protein C resistance may be due to genetic mutations such as factor V Leiden
G1691A. This and other point mutations such as prothrombin G20210A offer genetic insights into
the pathogenesis of hypercoagulable states. It is also interesting to note the ethnic differences in
the prevalence of these mutations, with the Western population suffering higher incidence than the
Eastern population, which may be the basis for racial differences in thrombotic risks,

Homocysteinemia
Case-control studies and meta-analyses have demonstrated that an increase in plasma
homocysteine is a significant independent risk factor for ischemic stroke Numerous genetic errors
in the metabolism of sulfur containing amino acids produce plasma hyperhomocysteinemia and
homocystinuria. Hyperhomoscysteinemia may activate coagulation via endothelial injury,
producing an occlusive vasculopathy Acquired conditions such as vitamin B12 and folate
deficiency, renal failure hypothyroidism, and drugs including anticonvulsants predispose to
hyperhomocysteinemia. Randomized controlled trials using folate and vitamin B supplements to
lower homocysteinemia are ongoing, but a National Institutes of Health-National Institute of
Neurological Disorders and stroke. (NI11 NINDS)-sponsored randomized trial failed to show
dose-dependent effects of folate and vitamin in reducing stroke risks.

Antiphospholipid antibodies and stroke

The presence of antiphospholipid antibodies has been associated with increased risk of strokes.
Clinical features of primary antiphospholipid syndrome (APLS) include recurrent migraine-like
headaches, fetal loss, mild thrombocytopenia, false-positive veneral Disease Research Laboratory
(VDRL) tests, and arterial or venous cerebrovascular events that may present with encephalopathy
Secondary APLS occurs with lupus erythematosus, immune complex diseases, cancer, and drug
reaction These patients have cither lupus anticoagulant or anti cardiolipin antibody of significant
tilers. By contrast, low- titer APIS is found in 1-2% of the normal population. it also occurs
transiently after infection, Tissue trauma including myocardial infarction or heart surgery), and
secondary to drugs and is usually not associated with thrombotic events. To prevent recurrent
stroke in patients ls with primary or secondary APLS is challenging. Warfarin is generally used.
Immunosuppression and the addition of aspirin to anticoagulation for individuals with recurrent
cerebral ischemia are therapeutic options However, these strategies are not evidence based.
Furthermore, the optimal length and intensity of anticoagulantion therapy are uncertain due to the
paucity of data about treatment outcomes.

Thrombotic thrombocytopenic purpura

Thrombotic thrombocytopenic purpura (TTP) is a consumptive coagulopathy characterized by
microangiopathic hemolytic anemia, thrombocytopenia, and central nervous system disorders
including ischemic strokes. Important pathophysiological changes occur in small arteries and
include platelet microthrombi, marked intimal hyperplasia, and fibrin deposits in the subintimal
parts of affected blood vessels, contributing to multiple organ damage, particularly the brain and
kidney Clinically, TTP may present with fluctuating encephlopathic signs and seizures. Computed
tomography (CT) or magnetic resonance imaging (MR) findings may show ischemic changes,
cerebral edema, or intra cerebral hemorrhage. Therapeutic measures include the use of high-dose
corticosteroids, repeated plasma exchanges, antiplatelet agents, and splenectomy, with varying
degrees success.

other coagulopathies
There are other rare genetic disorders that may predispose carriers to hypercoagulable states. These
hereditary diseases that affect clotting mechanisms include defect in heparin cofactor II and
fibrinolysis factors such as plasminogen, tissue plasminogen activator, and excessive formation of
plasminogen activator inhibitor-1. The role of these rare hereditary conditions in venous
thrombosis and stroke remains to be defined. An acquired hypercoagulopathy is frequently found
in cancer patients who may have increased risk of thrombotic vascular disorders including stroke.
Detailed description of the hypercoagulable state in malignancy is beyond the scope of this chapter.