What is the appropriate evaluation of cryptogenic stroke, and when is a hypercoagulability work-up needed? David E. Thaler, MD, PhD, FAHA

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1 What is the appropriate evaluation of cryptogenic stroke, and when is a hypercoagulability work-up needed? David E. Thaler, MD, PhD, FAHA Neurologist in Chief, Tufts Medical Center Professor and Chair of Neurology, Tufts University School of Medicine Boston, MA

2 Disclosure Statement of Financial Interest Within the past 12 months, I have had a financial affiliation with the organization(s) listed below. Affiliation/Financial Relationship Grant/Research Support Consulting Fees/Honoraria Major Stock Shareholder/Equity Royalty Income Ownership/Founder Intellectual Property Rights Other Company Steering Committee, RESPECT Trial, Abbott All content provided by Dr David Thaler unless otherwise noted.

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4 What is the appropriate evaluation of cryptogenic stroke, and when is a hypercoagulability work-up needed? David E. Thaler, MD, PhD, FAHA Neurologist in Chief, Tufts Medical Center Professor and Chair of Neurology, Tufts University School of Medicine Boston, MA

5 What is the appropriate evaluation of stroke, and when is a hypercoagulability work-up needed? David E. Thaler, MD, PhD, FAHA Neurologist in Chief, Tufts Medical Center Professor and Chair of Neurology, Tufts University School of Medicine Boston, MA

6 What is the underlying mechanism? Stroke is an observation not a diagnosis

7 Common mechanisms of cerebral ischemia Small vessel disease, lacune (lipohyalinosis) Embolism Artery-to-artery (carotid, aorta, other) Cardiac source Paradoxical Decreased perfusion through a fixed stenosis

8 Lacunar stroke (0.2-15mm 3 )

9 Large, old stroke

10 Other causes of cerebral ischemia Vasculitis Collagen vascular diseases: isolated angiitis of the CNS, temporal (giant cell) arteritis, polyarteritis nodosa, Wegener's granulomatosis, Takayasu's arteritis, syphilis Meningitis: tuberculosis, fungi, syphilis, bacteria, herpes zoster Arterial dissection: carotid, vertebral, basal intracranial arteries Hematologic disorders: polycythemia, thrombocytosis, thrombotic thrombocytopenic purpura, disseminated intravascular coagulation, dysproteinemias, hemoglobinopathies (sickle cell disease) Miscellaneous: cocaine, amphetamines, moyamoya disease, fibromuscular dysplasia, CADASIL Hypercoagulable states: secondary to systemic disease, carcinoma (especially pancreatic), eclampsia, oral contraceptives, lupus, factor C or S deficiency, factor V mutation, etc. Vasospasm: following subarachnoid hemorrhage Reversible cerebral vasoconstriction: idiopathic, migraine, eclampsia, trauma Venous: Dehydration, pericranial infection, postpartum and postoperative states, systemic cancer

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15 <50y 51-84y

16 Arterial hypercoagulable testing Lupus anticoagulant Anticardiolipin Ab Beta-2 glycoprotein Homocysteine

17 If venous infarction or R-L shunt identified Arterial hypercoagulable testing Lupus anticoagulant Anticardiolipin Ab Beta-2 glycoprotein Homocysteine Venous hypercoagulable testing Protein C, protein S, anti-thrombin III (RARE!) Prothrombin gene mutation Factor V Leiden (activated protein C resistance) Factor VIII

18 If venous infarction or R-L shunt identified Arterial hypercoagulable testing Lupus anticoagulant Anticardiolipin Ab Beta-2 glycoprotein Homocysteine Venous hypercoagulable testing Protein C, protein S, anti-thrombin III (RARE!) Prothrombin gene mutation Factor V Leiden (activated protein C resistance) Factor VIII If unexplained BILATERAL embolic infarcts

19 If venous infarction or R-L shunt identified Arterial hypercoagulable testing Lupus anticoagulant Anticardiolipin Ab Beta-2 glycoprotein Homocysteine Venous hypercoagulable testing Protein C, protein S, anti-thrombin III (RARE!) Prothrombin gene mutation Factor V Leiden (activated protein C resistance) Factor VIII If unexplained BILATERAL embolic infarcts cancer?

20 Stroke, cancer, d-dimer, and mortality Baseline d-dimer and mortality Journal of Stroke (1) Treated d-dimer and mortality

21 CONCLUSIONS Rely on neurology to make a stroke diagnosis Tailor testing to individual patient characteristics Making a diagnosis is changing management