Transcript
Page 1: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

HematologyAjay Zachariah, MD

11/20/2014

Page 2: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

Venous ThromboembolismDVT and PE

Page 3: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

Venous Thromboembolism

VTE

DVT: Deep vein thrombosis

PE: Pulmonary embolus

Clinical Risk Factors

Virchow’s Triad

Stasis

Endothelial injury

Hypercoagulability

Other

Familial thrombophilia

Obesity

Previous clot

Malignancy

Pregnancy/postpartum

Page 4: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

Rudolph Virchow (1821-1902)

Discounted the Theory of Humors

Introduced science to medicine

Father of Modern Pathology

Page 5: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

Deep Vein ThrombosisPre-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 Baker’s) 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

Well’s 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)

Page 9: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

Deep Vein Thrombosis

Well’s Criteria: Quantified Pretest Probability of DVT (con’t)

≥ 3: High Probability

1-2: Moderate Probability

0: Low Probability

Page 10: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

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)

Page 11: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

Source: Up To Date

Page 12: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

Know your allergies…

Page 13: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

Pulmonary EmbolismPre-test Probability and Diagnosis

Page 14: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

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

Page 15: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

Pulmonary Embolism: Diagnosis

Modified Well’s 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)

Page 16: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

Pulmonary Embolism: Diagnosis

Modified Well’s Criteria: Quantified Pretest Probability of PE (con’t)

>6: High

2-6: Moderate

<2: Low

Page 17: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

Pulmonary Embolism: Diagnosis

Diagnosis: Base on pretest probability

Low: Check D-dimer

Low: Rules out PE

High: Check Spiral CT

Moderate or High:

Pulmonary angiography (gold standard): not recommended as first choice imaging

Spiral CT: High sensitivity and specificity

Page 18: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

Pulmonary Embolism: V/Q Scan

Ventilation/Perfusion Lung Scan Uses medical isotopes to evaluate flow of blood and air in the lungs.

Indications: renal failure, contrast allergy

V/Q Scan Probability Results [PIOPED (1994): 933 patients] Normal: Rules out PE regardless of Well’s score

Low

4% chance of PE

If low Well’s score, PE ruled out

High

95% chance of PE

If high Well’s score, PE confirmed

All other combinations equivocal

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Pulmonary Embolism: V/Q Scan

V/Q Normal V/Q Low V/Q High

Well’s Low PE Ruled out PE Ruled out Equivocal

Well’s Mod PE Ruled out Equivocal Equivocal

Well’s High PE Ruled out Equivocal PE Confirmed

Equivocal requires either angiography or other imaging.

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Next June…

Page 21: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

Management of VTEFurther Work-up and Treatment

Page 22: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

Further Work Up After VTE Diagnosis

Malignancy

Patient has 1.3x expected cancer risk

Work up for cancer:

Complete H&P

Rectal and pelvic exams

Labs: CBC, LFT’s, CXR, stool guaiac

Patient will NOT need aggressive cancer screening

Thrombophilia

Screen if diagnosed prior to age 50

History: Family, past VTE

Unusual vascular beds

Warfarin-induced skin necrosis

Labs: Protein C/S, fibrinogen, antithrombin III, Factor V Leiden, Lupus anticoagulant, anticardiolipin, prothrombin gene mutation

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Warfarin-Induced Skin NecrosisAcquired protein C deficiency from Warfarin use

Page 24: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

Treatment of VTE

Treatment is usually outpatient

Criteria for inpatient treatment

Massive DVT

Symptomatic PE

High bleeding risk

Co-morbidities requiring hospitalization

Contraindications

Active Hemorrhage

Platelets < 50,000

Prior history of intracerebral hemorrhage

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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.

Page 26: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

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

Page 27: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

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

Page 28: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

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

Page 29: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

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.

Page 31: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

When placing a foley…

Page 32: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

VTE in PregnancyDiagnosis 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

Hampton’s Hump: Wedge opacity

Normal: Perform V/Q scan

Abnormal: Perform CT

Page 35: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

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

Page 36: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

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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AnemiaCauses and Features to Evaluate

Page 39: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

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)

Page 40: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

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)

Page 41: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

Workup: Morphologic Approach

Macrocytic

MCV > 100

Causes

B12/folate deficiency

Myelodysplasia

EtOH abuse

Liver disease

Hypothyroidism

Page 42: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

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)

Page 43: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

Workup: Morphologic Approach

Normocytic

MCV 80-100

Causes

Acute blood loss

Acute hemolysis

Hypersplenism

Chronic Illness

Page 44: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

Iron Deficiency Anemia

Iron Studies

Low Iron

High TIBC

Low Ferritin

Causes

Low intake

Chronic Blood loss

Menstrual

GI (malignancy or otherwise)

Page 45: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

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

Page 46: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

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

Page 47: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

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

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Sickle Cell DiseasePathology 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

Page 50: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

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

Page 51: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

Sickle Cell Disease: Complications

Infection

Pneumococcus

Haemopilus

Salmonella

Aplastic crisis from Parvovirus B19 bone marrow suppression

Acute chest syndrome

Pneumonia

Infarct

Page 52: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

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

Page 53: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

HemophiliaGenetics and Pathology

Page 54: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

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

Page 55: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

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

Page 56: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

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

Page 57: Hematology Ajay Zachariah, MD 11/20/2014. Venous Thromboembolism DVT and PE

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


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