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Hematology Ajay Zachariah, MD 11/20/2014

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Venous Thromboembolism DVT and PE

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Venous Thromboembolism VTE DVT: Deep vein thrombosis PE: Pulmonary embolus Clinical Risk Factors Virchows Triad Stasis Endothelial injury Hypercoagulability Other Familial thrombophilia Obesity Previous clot Malignancy Pregnancy/postpartum

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Rudolph Virchow (1821-1902) Discounted the Theory of Humors Introduced science to medicine Father of Modern Pathology

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Deep Vein Thrombosis Pre-test Probability and Diagnosis

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Deep Vein Thrombosis Symptoms Pain and swelling of an extremity Usually lower extremity

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Deep Vein Thrombosis Differential Diagnosis Cellulitis: chemical (ex, with venous insufficiency) or bacterial Superficial thrombophlebitis: palpable, tender, superficial veins Venous valvular insufficiency: associated with past history of DVT Lymphedema: usually chronic problem Popliteal (AKA Bakers) Cyst Distention of the bursa or posterior herniation of joint capsule, likely leaking/ruptured, causing calf swelling. Can be concurrent with DVT if popliteal vein is compressed Knee Joint Pathology: (e.g. ACL tear) can cause unilateral pain, inflammation, swelling Drug-educed edema: Ex. CCBs. Calf muscule pull/tear: i.e. Non-Achilles tendon injury

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Deep Vein Thrombosis Wells Criteria: Quantified Pretest Probability of DVT Cancer: Treatment within last 6 months (+1) Paralysis/weakness/immobilization of LE (+1) Bedridden for > 3 days OR major surgery in past 4 weeks (+1) Tenderness along deep veins (+1) Entire leg swollen (+1) Calf swollen > 3 cm compared to asymptomatic leg (+1) Pitting edema in affected leg (+1) Collateral non-varicose superficial veins (+1) Alternative diagnosis more likely (-2)

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Deep Vein Thrombosis Wells Criteria: Quantified Pretest Probability of DVT (cont) 3: High Probability 1-2: Moderate Probability 0: Low Probability

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Deep Vein Thrombosis Diagnosis: High Pretest Probability Perform Venous Compression Ultrasound If negative, repeat in 5-7 days Moderate Pretest Probability Perform Venous Compression Ultrasound Low Probability Check D-dimer to RULE OUT DVT D-dimer Sensitivity: 95% Specificity: 40-60% Venous Compression Ultrasound 94% Positive Predictive Value (chance that a positive result is a true positive)

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Source: Up To Date

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Know your allergies

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Pulmonary Embolism Pre-test Probability and Diagnosis

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Pulmonary Embolism: Diagnosis Symptoms Non-specific EKG, CXR, symptoms, physical findings. Pulse Ox, pO2 not particularly useful Classic symptoms Pleuritic chest pain Dyspnea Tachycardia Hemoptysis Cough Symptoms of DVT

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Pulmonary Embolism: Diagnosis Modified Wells Criteria: Quantified Pretest Probability of PE Symptoms of DVT (+3) Other diagnosis less likely (+3) HR > 100 (+1.5) Immobilization or surgery in last 4 weeks (+1.5) Previous DVT/PE (+1.5) Hemoptysis (+1) Malignancy (+1)

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Pulmonary Embolism: Diagnosis Modified Wells Criteria: Quantified Pretest Probability of PE (cont) >6: High 2-6: Moderate

Treatment of VTE Lovenox (LMWH) (> Unfractionated Heparin) Decreased mortality/bleeds Greater duration of action Lower risk of HIT No monitoring Contraindications: Pork allergy (Lovenox made from intestinal mucosa of pigs) Unfractionated heparin Monitor aPTT: must be between 1.5 and 2.5 Monitor platelets: HIT Heparin can be made from pig intestines or cattle lungs.

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Treatment of VTE Warfarin Start on day 1 of treatment INR must be therapeutic (2.0-3.0) for > 24 hours (i.e. two consecutive measurements) before stopping Lovenox Duration of Treatment First VTE 3-6 months Recurrent VTE: >12 months

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Treatment of DVT Compression stockings Start within 1 month, then continue for at least 1 year Prevention of post-thrombotic syndrome (~50% incidence) Pain Heaviness Itching/tingling Edema Varicose veins Skin discoloration Ulcers

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Treatment of DVT Duration of therapy (first time) Unprovoked Calf: 3 months Proximal (above propliteal vein): 3-6 months Provoked DVT Do not exceed 3 months

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Treatment of PE Hemodynamic stabilization Maintain oxygenation IVC Filter if anticoagulation is contraindicated Can be done as outpatient if patient stable and does not require supp. O2 Indications for thrombolysis or embolectomy Strong indication: Hemodynamically unstable Weak indications Right ventricular dysfunction ("submassive PE") Cardiopulmonary resuscitation Extensive clot burden: large perfusion or extensive embolus Severe hypoxemia Free-floating right atrial or ventricular thrombus Patent foramen ovale

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Treatment of PE Newer anticoagulants: studies in progress, no labs, no antidote Pradaxa: Direct thrombin inhibitor Xarelto: Factor Xa inhibitor Duration of therapy (first time) Unprovoked: 3-6 months Provoked: Do not exceed 3 months.

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When placing a foley

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VTE in Pregnancy Diagnosis and Treatment

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Epidemiology of VTE in Pregnancy Risk Increases 5x with pregnancy 1/1600 pregnancies Period of risk is both before AND after delivery PE most common post partum If pregnant woman has VTE, 20-50% have underlying thrombophilia VTE increases risk 3-4 times for subsequent pregnancies

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PE in Pregnancy Evaluation Do not use d-dimer due to persistent elevation Aim is to reduce radiation exposure First, perform CXR (ACOG guidelines) Looking for Westermark Sign: Vessel collapse Hamptons Hump: Wedge opacity Normal: Perform V/Q scan Abnormal: Perform CT

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VTE Teatment in Pregnancy Heparin and Lovenox do not cross placental barrier. Heparin: Increase dose due to binding proteins, renal clearance, etc Lovenox: Increase dosing interval due to longer half life. Warfarin crosses the placental barrier Highly teratogenic. DO NOT USE during pregnancy. Breast feeding Anticoagulants do not cross into breast milk

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VTE Teatment in Pregnancy Start with Lovenox Convert to unfractionated heparin during last month of gestation After delivery Start with compression stockings Vaginal delivery: restart anticoagulation after 4-6 hours C-section: restart anticoagulation after 6-12 hours Warfarin for 6 weeks to 6 months

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Overly-attached vertebral body

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Anemia Causes and Features to Evaluate

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Causes: Kinetic Approach Decreased RBC production Deficiency of substrate (e.g. iron, protein) Suppression/disorder of marrow (e.g. anti-neoplastics, myelodysplasia) Decreased hormonal stimulation (i.e. erythropoietin) Chronic illness (i.e. anemia of chronic disease) Increased RBC destruction Hemolysis Inherited (e.g. sickle cell) Acquired (e.g. CLL, SLE) Bleeding Occult (e.g. UGIB) Obvious (e.g. trauma)

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Workup: Morphologic Approach CBC Mean Corpuscular Volume (MCV) Mean Corpuscular Hemoglobin (MCH) Mean Corpuscular Hemoglobin Concentration (MCHC) Hypochromic (e.g. iron deficiency) Normochromic (e.g. B12 deficiency) Hyperchromic (e.g. hereditary spherocytosis, sickle cell disease) Red Cell Distribution Width (RDW) High RDW = anisocytosis Used to indicate mixed causes (e.g. iron deficiency + B12 defiency)

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Workup: Morphologic Approach Macrocytic MCV > 100 Causes B12/folate deficiency Myelodysplasia EtOH abuse Liver disease Hypothyroidism

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Workup: Morphologic Approach Microcytic MCV < 80 Causes Iron Deficiency Decreased Heme Synthesis Lead toxicity Sideroblastic anemia Decreased Globin Synthesis Thalassemia Hemoglobinopathy Chronic Illness Unlikely but possible More likely to be normocytic)

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Workup: Morphologic Approach Normocytic MCV 80-100 Causes Acute blood loss Acute hemolysis Hypersplenism Chronic Illness

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Iron Deficiency Anemia Iron Studies Low Iron High TIBC Low Ferritin Causes Low intake Chronic Blood loss Menstrual GI (malignancy or otherwise)

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Iron Deficiency Anemia Treatment FeSO4 325mg PO TID Duration: 3 months after H/H is normal Increase absorption Acids Vitamin C Avoid Calcium, Magnesium, Tea Caution patient about nausea, constipation, dark stools

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Megaloblastic Anemia Causes Deficiency: B12, Folate Elevated: Methylmalonic acid Symptoms/Signs Glossitis Anorexia Diarrhea Signs of Posterior Column Degeneration (with B12 deficiency) Paresthesias Ataxia Weakness Upward Babinski

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ER Hires Dilaudid Nazi to Dispense (or not) Dispense Narcotics

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Sickle Cell Disease Pathology and Management

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Sickle Cell Disease: Pathology Hemoglobin S Diagnostic of disease Detected with hemoglobin electrophoresis Genetics Homozygous: Sickle Cell Disease Heterozygous: Sickle Cell Trait Sickling Poor solubility when HbS is deoxygenated Polymerization of HbS, deforming RBCs Presents in life after fetal hemoglobin has decreased

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Sickle Cell Disease: Complications Anemia Elevated reticulocytes MCV normal/high Causes Intravascular hemolysis Splenic Sequestration: sudden acute anemia Vaso-occlusive events Muscular pain CVA Renal infarction Priapism Retinopathy

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Sickle Cell Disease: Complications Infection Pneumococcus Haemopilus Salmonella Aplastic crisis from Parvovirus B19 bone marrow suppression Acute chest syndrome Pneumonia Infarct

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Sickle Cell Disease: Management Immunizations Strep. pneumoniae Neisseria meningitidis H. influenzae, type B (HiB) Hepatitis B Annual Influenza Antibiotics Prophylaxis Age 3 months to 3 years: Penicillin V PO 125mg BID Age 3 years to 5 years: Penicillin V PO 250mg BID > Age 5: Case-by-case. Discuss with specialist

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Hemophilia Genetics and Pathology

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Hemophilia X-linked recessive: Predominantly affects males Types Hemophilia A: Factor VIII Deficiency Hemophilia B: Factor IX Deficiency Usually first symptoms occur before age 2 Not always diagnosed at circumcision Bleeding Muscles Hematuria GI Epistaxis/oral Joints: leads to arthritis Can be treated with factor concentrates

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Thrombotic Thrombocytopenic Purpura (TTP) Causes, Pathology, and Treatment

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Thrombotic Thrombocytopenic Purpura (TTP): Causes Usually idiopathic Shiga-like toxin from E. Coli 0157:H7 ADAMTS13 (vWF protease) Deficiency Causes platelet aggregation Medications Ticlopidine Plavix Quinine Mitomycin Tacrolimus

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Thrombotic Thrombocytopenic Purpura (TTP): Pathology and Treatment Classic Pentad Thrombocytopenia Hemolytic Anemia (caused by microangiopathy) Acute renal dysfunction Neurologic Symptoms Fever Curative treatment with plasma exchange therapy