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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
Rudolph Virchow (1821-1902)

Discounted the Theory of Humors

Introduced science to medicine

Father of Modern Pathology
Deep Vein Thrombosis
Pre-test Probability and Diagnosis
Deep Vein Thrombosis

Symptoms

Pain and swelling of an extremity

Usually lower extremity
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
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)
Deep Vein Thrombosis

Well’s Criteria: Quantified Pretest Probability of DVT (con’t)

≥ 3: High Probability

1-2: Moderate Probability

0: Low Probability
Deep Vein Thrombosis

Diagnosis:


High Pretest Probability

Perform Venous Compression Ultrasound

If negative, repeat in 5-7 days
Moderate Pretest Probability


Low Probability



Perform Venous Compression Ultrasound
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)
Source: Up To Date
Know your allergies…
Pulmonary Embolism
Pre-test Probability and Diagnosis
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
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)
Pulmonary Embolism: Diagnosis

Modified Well’s Criteria: Quantified Pretest Probability of PE (con’t)

>6: High

2-6: Moderate

<2: Low
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
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
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.
Next June…
Management of VTE
Further Work-up and Treatment
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
Warfarin-Induced Skin Necrosis
Acquired protein C deficiency from Warfarin use
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
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.
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
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
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
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
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.
When placing a foley…
VTE in Pregnancy
Diagnosis and Treatment
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
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
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
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
Overly-attached vertebral body…
Anemia
Causes and Features to Evaluate
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)
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)
Workup: Morphologic Approach

Macrocytic

MCV > 100

Causes

B12/folate deficiency

Myelodysplasia

EtOH abuse

Liver disease

Hypothyroidism
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)
Workup: Morphologic Approach

Normocytic

MCV 80-100

Causes

Acute blood loss

Acute hemolysis

Hypersplenism

Chronic Illness
Iron Deficiency Anemia


Iron Studies

Low Iron

High TIBC

Low Ferritin
Causes

Low intake

Chronic Blood loss

Menstrual

GI (malignancy or otherwise)
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
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
ER Hires ‘Dilaudid Nazi’ to
Dispense (or not) Dispense
Narcotics
Sickle Cell Disease
Pathology and Management
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
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
Sickle Cell Disease: Complications

Infection

Pneumococcus

Haemopilus

Salmonella

Aplastic crisis from Parvovirus B19 bone marrow suppression

Acute chest syndrome

Pneumonia

Infarct
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
Hemophilia
Genetics and Pathology
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
Thrombotic Thrombocytopenic
Purpura (TTP)
Causes, Pathology, and Treatment
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
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