McLeod Heme Tovee Class

8/6/2019 McLeod Heme Tovee Class

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MCCQE Hematology Review

Anne McLeod e-mail [email protected]

Office 416-340-3395


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GOALS and OUTLINE

Review MCCQE objectives and samplequestions

Few blood films

Few things not in the objectives

Practice questions


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MCCQE OBJECTIVES

www.mcc.ca/ObjectivesObjectives listed alphabetically

Practice Questions

-Exams-Mccqe1-Getting started-Practice exams

Two types of sample questions: MCQand CRS


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MCCQE OBJECTIVES

Bleeding tendency/bruising (#15-1)

Hypercoagulable state (#15-2)Anemia (#42-1)

Polycythemia/Elevated Hemoglobin (#42-2)

White blood cell abnormalities (#120)

Lymphadenopathy (#54)

Splenomegaly (#2-3)


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Bruising & Bleeding-History

Pattern - lifelong or recent, deepseated bleeds or superficial bruisingand petechiae

Bleeding challenges- circumcision,tonsils, wisdom teeth, menstruation,pregnancy, appendix

Other PMHx - cancer, renal or liverdisease


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Bruising & Bleeding-Hx and Px

Family history - bleeding or transfusion

Drugs - ASA, NSAIDS, alcohol and herbals

Check for the spleen, petechiae/purpura,

telangiectasia and evidence other systemicdisease


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HEMOSTASIS

Three steps:

1. Primary Hemostasis

Vascular response, platelets and *vWF

2. Secondary Hemostasis

Fibrin clot formation (coag cascade) *vWF*carrier for FVIII

3. Fibrinolysis


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VWF

VWF

VWF

VWF

VWF

VWF

VWF

VWF =von Willebrand Factor

Subendothelium

VWF

VWF

VWF

VWFVWFVWF

VWFVWF

PRIMARY HEMOSTASIS


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Subendothelium

HEMOSTASIS

2. Secondaryhemostasis - fibrin clot

1. Primary hemostasis-platelet plug


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Subendothelium

HEMOSTASIS

3. Fibrinolysis andwound healing


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PRIMARY HEMOSTASIS-Vessel

HEREDITARY: HHT (Osler-Rendu-Weber)

Connective tissue (Ehler-Danlos)

ACQUIRED: Drugs -Steroids

Senile purpura

Infections

Vasculitis


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PRIMARY HEMOSTASIS-Platelets

Too few platelets-thrombocytopenia

Dont work- platelet dysfunction


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PRIMARY HEMOSTASIS-Thrombocytopenia

DECREASED

PLATELETPRODUCTION

INCREASED

PLATELETDESTRUCTION

SEQUESTRATION

ie. plateletsstuck in thespleen/liver


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Accelerated Platelet Destruction

Non-immune-DIC, sepsis

Immune- TTP, ITP, SLE, drugs(heparin, quinidine,cephalosporins)

Look at the blood film/smear!!


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HIT

Platelet

Activated

Heparin-PF4

Complex

HIT Antibody


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Treatment of HIT Any heparin or LMWH contraindicated

in HIT

Need to use an alternative like a directthrombin inhibitor eg. Hirudin orargatroban

Warfarin may worsen the thrombosis ifnot overlapped with an alternativeanticoagulant until therapeutic


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Venous Limb Gangrene


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Confusing PLATELET

Problems

ITP HIT

PlateletPlatelet Platelet

UnControlled

vWF Release+

TTP

ActivatedActivatedNo activation


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Platelet Dysfunction1. Congenital-rare

2. Acquired COMMON!

Drugs - ASA, NSAIDs, Anti-Platelet agentsAlcohol, Uremia

Liver disease

Bone marrow disorders eg. MPD, MDS,MM


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Von Willebrands Disease Disorder of Primary ( Increased BT) and

Secondary hemostasis (Increased PTT)

Treatment DDAVP if mild disease, HemateP ( blood product with lots of VWF) ifsevere

Test family members usually autosomaldominant


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HEMOSTASIS SCREEN

Primary Hemostasis

CBC

Blood film/smear

Bleeding time

Platelet function tests

Tests for vWD


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HISTORY tells you :

PRIMARY SECONDARY

HEMOSTASIS HEMOSTASIS

Surface cuts Prolonged Normal

Onset after injury Immediate Delayed

Typical type / site Superficial Deep

Petechiae, purpura Subcutaneous

Mucosal bleed: Bleed into:

Nose, mouth, gums Joints, muscles,GI tract, Uterus GI /GU tracts

Post op/trauma


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CLOT

GENERATION

OF

THROMBIN

EXTRINSIC(TISSUE FACTOR)

PATHWAY

INTRINSIC

PATHWAY

Secondary Hemostasis


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Disorders of Secondary Hemostasi

Hereditary

Hemophilia A (factor VIII deficiency) andHemophilia B (factor IX deficiency) are X-linked and produce hemarthroses andhematomas and are treated withrecombinant factor concentrates or if mild

deficiency DDAVP

von Willebrands disease


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Disorders of Secondary Hemostasis

Acquired

vitamin K deficiency (factors II, VII, IX and

X)

liver disease (all factors other than VIII)

DIC

Inhibitors Drugs- warfarin, heparin


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Standard Heparin

Usually administered in hospital becausecareful monitoring required if given IV

Aim is to achieve an aPTT of 2.5-3X normalie. 60-90s

IV bolus followed by continuous infusion

Short half-life once IV infusion stoppedaPTT normalizes in ~4 hrs


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Standard Heparin

Easy to over anticoagulate patientswhich carries a very high risk ofbleeding

Standard heparin can be reversed by

protamine


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Warfarin


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Warfarin

Vitamin K antagonist

Rapidly absorbed from GI tract buttakes few days to be therapeutic

Dosing varies

Very close monitoring of INR required

in first few weeks

Dont start without heparin also!


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Treatment of Warfarin Overdose

Vitamin K -works in 6-12 hrs

Fresh frozen plasma- worksimmediately but BLOOD PRODUCTuse if life threatening bleeding only!!!

Careful monitoring of INR best way to

prevent bleeding


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Extrinsic Pathway

PROTHROMBIN TIME - PT /INR

Increased if deficiency of factor VII and also of

common pathway factors- X, V, II and fibrinogen.

Results also reported as INR - to allow for

standardization between laboratories.

Used for monitoring oral anticoagulant (Warfarin)

therapy.


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Intrinsic Pathway

ACTIVATED PARTIAL THROMBOPLASTIN TIME

- aPTT

Detects deficiencies of the intrinsic

pathway factors XII, XI, IX, VIII and also

common pathway X, V, II and fibrinogen.

Used to monitor anticoagulation therapy

with standard heparin.


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50/50 MIX

PT/INR or PTT prolonged

Rule out presence of warfarin or heparin

If corrects=factor deficiency

If doesnt correct=inhibitor


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HEMOSTASIS SCREEN

THROMBIN CLOTTING TIME - TT

A test for conversion of fibrinogen to fibrin

Detects fibrinogen deficiency

Detects abnormal fibrinogens - dysfibrinogenemia

Detects inhibitors of fibrin polymerization - FDPs

(Fibrin degradation products) or D-dimers.

Detects thrombin inhibition eg. Heparin


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Quiz-Treatment of Bleeding Platelet transfusions

Vitamin K

Antifibrinolytics

DDAVP

FFP and cryoprecipitate

Protamine sulphate


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Sample Questions-MCQ

Which of the following is true about

hemorrhagic disease of the newborn:

Results from Vit K deficiency

More common in females

More common in bottle fed infants

Requires treatment with FFP

Evident in the first 24 hrs of life


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Sample Questions-MCQ Mr H has hemophilia which is shown to be due to anti-

hemophilic globulin deficiency. There is no hemophilia

in his wifes family. He has 4 sons and 4 daughters.

Which is true?:

0 sons have H, 2 daughters carriers

4 sons H, 2 daughters carriers

0sons

H,0

daughters carriers 0 sons H, 4 daughters carriers

2 sons H, 4 daughters carriers


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Made up question- CRS A 65 year old man is admitted with loss of

consciousness a few hours after a fall. He had been

experiencing a flu-like illness for several days

according to his daughter. CT head shows a subdural

hematoma and he requires urgent surgery.

According to his daughter he takes several heart pillsand she tells you he had surgery to replace his heart

valve 6 yrs ago.


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Made up question- CRS

You are called by the lab : Hb 100

MCV 95 WBC 12 Plts 350 INR 8.0

aPTT 55 Fibrinogen N Creat LFT N.

What do you think is the most likely

cause of the elevated INR?


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What are you going to do prior to his

surgery? Choose 3 Transfuse pRBC

Transfuse platelets

Give FFP

Give cryoprecipitate

Give Vit K

Give protamine

Cross and type forpRBC

Give DDAVP


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After treatment the

surgeons want to

know if he can go to

the OR now what

blood tests will you

do? Choose 2 or

choose NONE:

INR and PTT

Thrombin time

CBC

INR

Heparin level

Warfarin level

Bleeding time

NONE


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MCCQE OBJECTIVESBleeding tendency/bruising (#15-1)

Hypercoagulable state (#15-2)

Anemia (#42-1)



Lymphadenopathy (#54)Splenomegaly (#2-3)


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Hereditary Causes of Thrombophilia

Antithrombin III

deficiency

Protein C deficiency

Protein S deficiency

Factor V Leiden

Prothrombin 20210


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Acquired Risk Factors for VTE Age

Previous thrombosis

Immobilization

Surgery

Malignancy

Nephrotic syndrome

APLA syndrome

Myeloproliferative

disorders

BCP / HRT

Pregnancy/postpartum

Obesity Heavy smoker


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Who should be screened?Hereditary

Age


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ThrombophiliaWorkup after H+PINITIAL

CBC

Screen forantiphospholipid antibody

Fasting homocysteine

APCR-functional screenfor Factor V Leiden

DNA testing for Factor VLeiden and Prothrombinmutations

POST HEPARIN

Antithrombin

POST WARFARIN

Protein C,S


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Diagnosis Physical exam not useful

D-dimers

Doppler ultrasound

Ventilation/Perfusion scan

CT chest with PE protocol

We dont use Impedanceplethysmography


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Treatment of VTE

Antiplatelet agents-Phlebitis only

Anticoagulants

- standard heparin

low molecular weight heparins

warfarin

new agents

Thrombolytic agents


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Sample Question-CRS 28 yr old G2P2 woman presents 5 days

post SVD with 2 day history of aching and

tenderness L inguinal region. L leg isdiscoloured and swollen. No othersymptoms she is breastfeeding.

What tests if any would you order choose

up to 3:


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Sample Question-CRS ABG

Blood culture

CBC Doppler US of leg

Ear oximetry

ECG

Endometrial culture

ESR

Fibrinogen leg scan

IPG

Pelvic US

PT, PTT Radionucleotide

phlebography of leg

Thermography of legs

Venogram L leg Vent/Perf scan

No tests


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Sample Question-CRS Pt admitted with

baby to start

treatment in 4-6hrs what orderswould you write?Choose up to 5.

Acetominophen

Aspirin daily

Antibiotics IV Bedrest

CXR

CBC

Daily IPG IVC filter


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Sample Question-CRS Heparin IM

Heparin IV bolus

Heparin by IV constantinfusion

Heparin SC

Initial PTT

PTT at 4 hrs post bolus Plt count q 3 days

Stop breastfeeding

Streptokinase

Support hose Surgery consult

Traction L leg

Tubal ligation

Vitamin K Warfarin


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Sample Question-CRS Patient treated to

prepare for

discharge whatwould you do?Choose as many aswant.

Avoid ASA Contraception

Support hose

Heparin 3-4 mons

Heparin 5-6 mons Reg PT and PTT

Reg PT

Stop breastfeeding

Vitamin K

Warfarin 3-4 mons Warfarin 5-6 weeks


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Anemia (#42-1)





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Approach to Anemia Focus on bleeding, drugs, family

history, diet and bowel habits

Look at MCV, WBC, diff, plts and film

New or old

MCV very helpful !!


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Approach to Anemia

Look at the blood film!!!

Micro Macro vs Normo


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Microcytic Anemia T

A

I

L

S

Look at the blood film!!!


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Iron Ferritin is the best blood test for assessing

iron stores but is increased by

inflammation, cancer and liver disease

Nail changes

Pica, blue sclerae, glossitis, angularstomatitis, sore burning mouth,esophageal web


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Iron - Clinical Points Blood film is usually diagnostic

Bone marrow examination is rarely needed

Iron deficiency is nevera final diagnosis The 10-10-1 rule

10 mg in diet

10% absorbed

1 mg absorbed and lost daily Consider Celiac disease


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Iron - Therapy Iron replacement requires normalization of

the hemoglobin and the body stores (3mons after hemoglobin normal)

Iron therapy is a balance between the doseof elemental iron and GI tolerance

Iron supplements are good forpremenopausal women and potentiallyharmful to men


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Anemia of Chronic Disease Common in patients with infection, cancer,

inflammatory and rheumatologic diseases

Iron can not be remobilized from storage Blunted production of erythropoietin and

response to erythropoietin

Usually normocytic and normochromic but

may be microcytic if severe


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Thalassemia Poikilocytosis and basophilic stippling may

be seen in the blood film

Hemoglobin electrophoresis is onlydiagnostic for beta-thalassemia and maynot be diagnostic if iron deficiency is alsopresent

Hb H prep and/or DNA analysis needed todiagnose alpha-thalassemia


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Sample Question Lead exposure can cause all of the

following except:

a) Abdo painb) porphyrinuria

c) Cirrhosis of the liver

d) Paresise) anemia


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Made up Question A woman with HB SC disease presents in

pregnancy. She asks if the baby will have

HB SC disease. Choose the correctanswer:

a) Baby can not have SC disease

b) Baby will have sickle cell trait

c) Baby will be normal

d) More information is needed


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Sideroblastic Anemia Produces a dimorphic blood film

with microcytes and macrocytes

Marrow shows ring sideroblasts

Usually acquired and associated witha myelodysplastic syndrome, drugs

or toxins Rarely due to pyridoxine deficiency


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Macrocytic AnemiaOval macrocytes (megaloblastic)

B12, folate, drugs

Round Macrocytes

Reticulocytosis

Alcohol/ Liver Disease

Myelodysplasia


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B12 Deficiency Be aware of the neurological

complications

Never treat possible B12 deficiencywith folate - the CNS lesions mayprogress

Schilling test distinguishes perniciousanemia from other causes


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Folic Acid Deficiency The peripheral blood film and bone marrow

are identical to B12 deficiency

Women of childbearing age should takesupplemental folate to prevent neural tubedefects in their children

Folate supplementation lowershomocysteine levels leading to less heartdisease and stroke


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Normocytic Anemia

Are the retics high or low?


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Normocytic AnemiaHigh Retics= making RBC butbeing lost

Bleeding

Hemolysis

MyelofibrosisTreated nutritional deficiency


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Hemolytic Anemia

Destruction of RBC leads to increasedretics, increased indirect bilirubin andincreased LDH

Hereditary or acquired


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Hemolytic AnemiaIntravascular RBCs being destroyed

in the blood vessel and hemoglobin

lostTests:

RBC fragments, decreased

haptoglobin, hemoglobinuria Become iron deficient over time


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Hemolytic AnemiaExtravascular hemolysis-RBCs being

destroyed by RE system and hemoglobinrecycled:

Autoimmune hemolytic anemia -like ITPantibody on surface of RBC destroyed tooearly by RE system

Test: Direct antiglobulin test (Coombstest),dont become iron deficient


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Hemolytic Anemia-Intra and Extra

Inherent RBC Defects

Membrane defects - hereditaryspherocytosis and hereditaryelliptocytosis

Enzyme defects - G6PD

Hemoglobinopathy - Sickle CellDisease


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Sample Question What would be the best test to confirm

the diagnosis of hereditary spherocytosis:

a) RBC enzyme studiesb) HLA studies

c) Bone marrow

d) Osmotic fragility

e) Coombs test


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Normocytic AnemiaLow Retics= not making RBC

Bone marrow problem-MDS,leukemia, cancer, aplasticanemia

EPO problem- uremia, ACDThyroid


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Anemia by ageMore common in elderly:

bone marrow problemsMDS,MM leukemias (CLL,CML, AML) Low

Kids get acute leukemias notchronic or MDS or MPD


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Made up question A 32 yr old woman presents with

few day history of easy bruising

and headache. CBC: Hb 135 MCV 95 WBC 12 Plt

3

What are you going to order? What is your diagnosis?


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Made up question A 32 yr old woman presents with

a 1 day history of petechiae andheadache.

CBC: Hb 85 MCV 99 WBC 12 Plt 3

What are you going to order?

What is your diagnosis?


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MCCQE OBJECTIVESBleeding tendency/bruising (#15-1)Hypercoagulable state (#15-2)

Anemia (#42-1)Polycythemia/Elevated Hemoglobin

(#42-2)White blood cell abnormalities (#120)



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Polycythemia/ Increased Hemoglobin

Increased Hgb may be due toincreased RBC mass or decreasedplasma volume

Need to measure red cell mass(blood volume studies)


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Increased Red cell mass Independent of EPO= Polycythemia

Rubra Vera (low EPO level)

Secondary to Increased EPOAppropriate EPO elevation ie. Hypoxemia,

Hb defects, carbon monoxide

Inappropriate EPO elevation ie. EPO

secreting tumours, polycystic kidneys, postrenal transplant, androgens


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Polycythemia Rubra Vera Must be differentiated from secondary

erythrocytosis and other MPD

Arterial and venous thromboses/ Bleeding Splenomegaly often massive

Increased neutrophil count and/or plateletcount is seen frequently

Treatment is phlebotomy or hydroxyurea


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Anemia (#42-1)Polycythemia/Elevated Hemoglobin (#42-2)

White blood cell abnormalities(#120)



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WBC DifferentialNeutrophils (ANC)

Lymphocytes

MonocytesEosinophils

Basophils

Left shifted- bands, myelocytes,metamyelocytes


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Leukemoid Reactions CML mimicked by acute bacterial infection

inflammatory reactions, severe marrow

stress such as bleeding, underlying tumorsand treatment with G-CSF and GM-CSF

CLL mimicked by pertussis, TB and mono

CMML and acute monoblastic leukemia

mimicked by TB


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Chronic Myeloproliferative Disorders Polycythemia rubra vera

Chronic granulocytic (myelogenous)leukemia

Idiopathic Myelofibrosis

Essential thrombocythemia


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Approach to Neutropenia History - drugs, toxins, recurring mouth

sores, family history, ethnic background

Physical - splenomegaly, bone pain If the patient is asymptomatic recheck the

WBC after exercise

Blood film - are granulocytic precursors or

blasts present Bone marrow

Severity significant (ANC< 500)


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Approach to Neutropenia (ANC


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Approach to Lymphocytosis

Young people think MONO

Old people CLL


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Infectious Mononucleosis Fever, pharyngitis, generalized adenopathy

splenomegaly and hepatomegaly

Monospot and EBV antibodies are positive immune thrombocytopenia and anemia

seen

the blood film shows atypical lymphs

with granules, coarse chromatin andspreading cytoplasm with pseudopods


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Chronic Lymphocytic Leukemia Common in the elderly

the blood film shows a lymphocytosis that

may be extreme and smudge cells lymphadenopathy and splenomegaly

Often complicated by autoimmune anemiaand thrombocytopenia

treatment is observation, alkylatingagents, fludarabine, steroids or radiation


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Multiple Myeloma The blood film shows rouleaux

a monoclonal immunoglobulin can be in

serum or urine Hypercalcemia, renal failure, lytic bone are

frequent

Treat hydration, steroids,

bisphosphonates, chemotherapy or BMT Need to distinguish from MGUS


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Lymphadenopathy (#5

4)Splenomegaly (#2-3)


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Is it LYMPHOMA?Ask about B symptoms- fever, night

sweats, weight loss

Is there evidence of infection?LNs-tender, size, consistency,

fixed/matted

Examine spleen

Always consider LN biopsy


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Made up Question-CRSA 70 yr old man presents with 6 month history of

fatigue, night sweats and weight loss. Examreveals diffuse adenopathy.

What investigations would you do first?Choose 2

a) CBC with differential

b) INR and PTT

c) Blood film/smear

d) CT thorax and abdo

e) Lymph node biopsy


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Lymphadenopathy (#54)

Splenomegaly (#2-3)


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SplenomegalySpleen should not be palpable in adults

Ask about B symptoms and look for LNs

Spleen exam- percussion most sensitive(JAMA paper)

Causes:

Infiltrative vs. Congestive vs. Increaseddemand for splenic function


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Sample Question-MCQ22 yr old man who had splenectomy 2 yrs ago

post trauma presents with confusion, coughand fever which developed over 12 hrs.

On arrival VS T 41 RR 28 BP 90/70HR 130

Which of the following would best confirm the diagnosis?

a) Blood culture

b) CXR

c) Sputum sampled) ECG

e) Urine culture


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Sample Question-MCQA 22 yr old woman presents with iron deficiency

anemia and easy bruising. Her INR/PT isnormal and PTT is slightly prolonged.

Which of the following is the most likely diagnosis?

a) DIC

b) Liver failure

c) Von Willebrand disease

d) Hemophilia A (factor VIII def)

e) Factor XII deficiency


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Sample Question-MCQA 30 yr old woman presents with a swollen left calf. She

has no family history of blood clots.Her INR/PT isnormal and her PTT is prolonged. Investigationsdemonstrate a DVT.

Which of the following is the most likely etiology of herDVT?

a) Von Willebrand disease

b) Antithrombin deficiency

c) APLA

d) Pregnancy

e) Age


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Sample Question-MCQA 60 yr old man with prostate cancer presents

with a painful swollen right leg.

Which of the following is the most appropriateinvestigation?

a) CXR

b) venogram

c) Doppler US of leg

d) D dimer

e) PSA


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MCCQE Hematology Review

Anne McLeod

e-mail [email protected]

Office 416-340-3395

Documents

McLeod Heme Tovee Class