Hematology update 2013

Hospital Ampang

Toh See Guan

Approach to thrombocytopenia

Step 1: Exclude platelet clumping

Case 1

Madam Chin, 60 year-old lady

Admitted with acute myocardial infarction

Platelet count 38 x 109/L

Streptokinase not given

Request platelet transfusion prior to antiplatelet therapy

Patient succumbed from CCF 1 week later

Pseudo-thrombocytopenia

Platelet clumping

Normal FBP

Urgency for specific therapy

Step 2: Exclude TTP/ APML

Case 2

32 year old stockbroker, male

Good health

Petechiae and purpura LL for 1 week

TW 8 Hb 11.5 Plt 14

Bilirubin 19

Commenced prednisolone for ITP

J Suriar 2012

Initial blood film

J Suriar 2012

Case 2- cont’d

Hb done a year ago 15.6

Presented to ED 1 week later with status epilepticus

Intubated and transferred to ICU

TW 13 Hb 9 Plt 14

Bilirubin 42 ID 38

LDH 2450

J Suriar 2012

Repeat blood film

J Suriar 2012

What is the diagnosis?

Thrombotic Thrombocytopenic Purpura (TTP)

1. Fever

2. Petechiae/ purpura

3. MicroAngiopathic Haemolytic Anaemia (MAHA)

4. CNS Symptoms confusion, seizures, stroke

5. Renal failureTTP plasma

Normal plasma

Idiopathic TTP

Acquired deficiency of ADAMTS13

Accumulation of HMW vW multimers

Disseminated small vessel thrombi

CNS predilection

Diagnosis is clinical

Mortality is high without appropriate management

Moake J. N Engl J Med 2002;347:589-600

Case 2- Progress

Plasma exchange

1 – 1.5 plasma volume, daily

Corticosteroids

Aspirin when plts > 50

Discharged on Day 14

Case 3 34 year-old lady

c/o fever and petechiae LL x 2 weeks

Hb 8.0 TW 39.3 Plt 18

Diagnosis: APML in DIC

Acute ProMyelocytic Leukaemia

Acute Promyelocytic Leukemia

Case 3- cont’d Treatment started on 5th July 2008:

ATRA 40 mg bd

iv dexamethasone 8 mg tds

iv idarubicin D1, D3, D5

In remission since

Drugs

Sepsis

Step 3: Exclude secondary causes

Case 4

29 yr old IDU

native tricuspid valve endocarditis

Blood culture : MRSA, IV vancomycin

commenced

Baseline FBC : TW 3 Hb 10 plt 280

After 5 days …

c/o gum bleeding

Plt 13

HIV serology negative

PBF confirms thrombocytopenia

BMAT normocellular

What is the cause?

Vancomycin- induced thrombocytopenia

How?

reduced production

increased destruction

Rx: stop offending drug

Drug-induced thrombocytopenia

Updated list

http://www.ouhsc.edu/platelets/ditp.html

Gradual and progressive in most

Rapid and severe in fiban type (e.g.tirofiban,

eptifibatide)

Case 5

52 year old farmer

Poorly controlled diabetes

Infected diabetic foot ulcer

Admitted with fever, hypotension, confusion

Hb 9.4 TW 12 plt 120

BU 9 Creat 130

Case 5- cont’d

Blood culture : Pseudomonas aeruginosa

Intubated for resp distress Day 3

TW 20.2 Hb 9 Plt 46

Creat 180 BU 10

PT 21 s APTT 39 s TT 20 sec

Fib 0.9 D dimer 35 ug/mL

What is the diagnosis?

1. Septicemia

2. Sepsis associated thrombocytopenia

3. Sepsis associated DIC - likely

Organ dysfunction

Case 6

61 F

NSTEMI June 2012

Referred to IJN from Hosp PD

Admitted for heart failure

Noted thyrotoxicosis

free T4>100 TSH 0.01

Case 6- cont’d

Noted plt low 61 on admission

Referred to haematology

Discharged from IJN with

Plavix, aspirin

Bisoprolol, nitrate, vasteral

Carbimazole

But no diuretics

Case 6- cont’d

Seen at haematology

JVP raised AB displaced, PSM at LLSE

PR: 110 AF Bilateral gross leg edema

Lungs: dull R side

Ascites ++

Hb 10 TW 6.7 Plt 75

Crea 35 BU 3.3

Case 6- Blood film

What caused the low platelet count?

Congestive cardiac failure

Liver congestion- reduced TPO

Splenic pooling

Uncontrolled thyrotoxicosis- immune

Drugs

Step 4: Exclude inherited thrombocytopenia

Case 7 28 year-old lady

G1 P0 @ 32 weeks

Referred for ITP in pregnancy

Case 7- cont’d O/E: Cushingoid

Hb 9.0 MCV 65 Plt 54

Delivered SVD

Blood loss: 700 mL

Transfused 2 PC

Steroids tapered off

Khong SY 2012

Case 7- cont’d 2 years later…

G2 P1 @ 18 weeks

Hb 8.8 Plt 51

Blood film

Case 7- bleeding history* Menorrhagia since menarche

Duration: 10 days

Soaks 5- 6 pads/day; double protection

Easy bruising since childhood

Case 7- family history 3 siblings- all in India

No f/h of bleeding

Parents are first cousins

Case 7- coagulation tests PT 13.4s

APTT 32.1s

Fibrinogen 4.1 g/L

FVIII 145%

vWF Ag 150%

Case 7- platelet aggregation

Patient % platelet aggregated

Normal control % platelet aggregated

51 x 109/L 150 x 109/L 50 x 109/L

Ristocetin 1.5 mg/mL 0 101 48

Collagen 0.19 mg/mL 30 84 34

ADP 2.0 x 10-5M 42 96 52

Arachidonic acid 5.0 mg/mL

38 72 42

Case 7- diagnosis Bernard-Soulier Syndrome

Deficiency of glycoprotein Ib/IX/V

Unable to bind to vWF

Failure in adhesion and aggregation

Case 8

30 F

G1 P0 @ 24 weeks

Noted Plt 52 Hb 11.7 TW 8.6

No h/o bleeding

May-Hegglin anomaly

Dohle body

A diagnosis of exclusion

Step 5: Consider diagnosis of ITP

Case 9

23 year-old lady

Presented in Feb 2012

c/o:

easy bruising x 3 months

gum bleeding

heavy PV bleeding

Case 9- cont’d O/E:

Pale+

Gum bleeding

Bruises + Petechiae LL

BP 119/74 PR 90

Other systems: NAD

Case 9- cont’d Hb 8.7 TW 4.5 Plt 12

MCV 65

Case 9- blood film

Case 9- cont’d

Started on steroids

1 week later, plt 50

Discharged

Causes of thrombocytopenia

Acquired

Reduced production AA, Leukaemia, MDS, etc

Increased destruction

Immune

- Drugs, ITP, HIT, etc

Nonimmune

- DIC, sepsis, TTP, HUS

Splenic sequestraction

- hypersplenism

Inherited

Take a good bleeding

history

Screen family

Approach to thrombocytopenia: 5 steps

Step 1: Exclude platelet clumping

Step 2: Exclude TTP/ APML

Step 3 Exclude secondary causes

Step 4: Exclude inherited thrombocytopenia

Step 5: Consider diagnosis of ITP

Thank you

The end