Hematology Emergencies: Problems with Platelets Emergencies: Problems with Platelets Christian...

Hematology Emergencies:

Problems with Platelets

Christian Cable, MD, FACP Associate Professor of Medicine

Division of Hematology & Oncology

Texas A&M HSC College of Medicine

Scott & White Healthcare

Fundamentals of Hospital Medicine

Temple, TX 1/11/2013

Learning Objectives

Recognize three distinct, scary

inpatient low platelet problems

Utilize relevant pathophysiology to

distinguish these entities

Enable participants to initiate

appropriate diagnostic and therapeutic

maneuvers

Disclosures

I love the blood

I am especially fond of platelets

I am not a vampire

I only take money from Scott & White,

American College of Physicians, and

my wife

The Call . . .

What could go wrong?

Copyright ©2001 American Society of Hematology. Copyright restrictions may apply.

Lazarchick, J. ASH Image Bank 2001;2001:100177

Figure 1. Large ecchymotic area over the thigh following minor trauma

Platelet Problems

Platelets in health

Why we bleed

ITP

TTP

HIT

Conclusions


Maslak, P. ASH Image Bank 2008;2008:8-00067

Figure 1. Granulocytes circulating in the blood of a patient with a normal peripheral smear

What is that?

1841 - - dust on the slide

Early 1900’s - - inert plug

Currently - - “inert but poised”

*metabolically active*


Maslak, P. ASH Image Bank 2005;2005:101353

Figure 1. The granular appearance of the platelets helps to distinguish them from artifact in the peripheral smear



Figure 1. Damage to the vascular endothelium results in recruitment of platelets which aggregate at the site, forming the primary hemostatic plug



Figure 2. Through the processes of adhesion, aggregation, and secretion, platelets successfully coalesce to complete the formation of the primary hemostatic plug



Figure 1. Secondary hemostasis involves the deposition of fibrin which results in fine clot formation

Hoffman Hematology, 5th

ed. Fig 114-7


ed. Fig 115-1

UpToDate, 17.1


ed. Fig 116-2

Nachman, NEJM Sept 18, 2008

Platelets . . .

. . . plug the holes.

Platelet Problems

Platelets in health

Why we bleed

ITP

TTP

HIT

Conclusions

Nachman, NEJM Sept 18, 2008

How low can you go?

Spontaneous Bleeding. . .

<10

Platelet Problems

Platelets in health

Why we bleed

ITP

TTP

HIT

Conclusions

CC: 39 weeks pregnant,

low platelets

26 y.o. woman

Modest bruising, close to delivery

CBC . . .



Figure 2. Peripheral smear in a patient with ITP showing an almost total absence of platelets

Fab

FCγ

Immune TP

Bromberg, NEJM Oct 19, 2006

When giants roamed

the halls . . .

ITP treatment

Decrease antibody production

Block antibody coated platelets from

being destroyed in spleen

Increase platelet production

Transfusion

Stimulate thrombopoeisis

ITP treatment

Steroids

IV immune globulin

Splenectomy

Platelet transfusions if bleeding

New agents to increase platelet

production

Success?

Platelet Problems

Introduction

Platelets in health

Why we bleed

ITP

TTP

HIT

Conclusions

CC: Seizure, low platelets

39 y.o. AA woman with known

seizures

To ER for recurrent seizures, bruising

on exam

CBC . . .



Figure 1. Peripheral smear showing microangiopathic hemolytic features with numerous RBC fragments (helmet cells/schistocytes)

Thrombotic TP

Microangiopathic hemolytic anemia +

thromobocytopenia is a very short list.

The list does NOT include ITP.

TTP is caused by an antibody directed

against a protease that cleaves the

vonWillebrand molecule. Longer vWF is

more sticky and causes platelets to stick in

small vessels. This causes multi-organ

ischemia and the shearing of red cells.

UpToDate, 17.1

Harrison’s, 17th ed. Fig 109-4

ADAMTS-13 protease

Fab

FCγ

CONTRAindications to

Transfusion

Platelets - - if the platelets are on fire,

don’t add more

TTP

HIT

x 48 treatments

Success?

Platelet Problems

Platelets in health

Why we bleed

ITP

TTP

HIT

Conclusions

NEJM 355;8 (809-17) August 24, 2006

In the Water?

HIT - - working diagnosis

A decrease in platelet count (<150K or

>50%) associated with heparin

exposure in a typical time course that

has a high risk of thrombotic (not

bleeding) complications which

requires alternative anticoagulation

upon diagnosis.

Heparin in the Hospital

Orthopedic Surgery

Cardiac Surgery

General Medical Patients

Acute Coronary Syndrome - - PCI

Acute Hemodialysis

Kids

Pregnancy

Chronic Hemodialysis

Types of Heparin

Unfractionated (15kDa~45 saccharide)

LMWH (5kDa ~ 15 saccharide)

Super LMWH (1.7 kDa

pentasaccharide)

Interact with AT and Xa to reverse

coagulation (Super LMWH just Xa)

How Heparin Works

WARNING - - clotting cascade

Tissue

Factor F VII


F VIIa F X


F Xa Prothrombin


Thrombin


Thrombin

Fibrinogen Fibrin


Thrombin

Fibrinogen Fibrin

Anti-thrombin


Thrombin

Fibrinogen Fibrin

Anti-thrombin

He

parin


Fibrinogen Fibrin

Thrombin Anti-thrombin

He

parin

Pathophysiology

PF4

Platelet

He

pa

rin

Pathophysiology

PF4

Platelet

He

pa

rin

Y

Y

Platelets coated by antibodies

Aggregate

(like a Coombs test)

Cleared by spleen

(thrombocytopenia)

Activated

(thrombosis) PF4

Platelet

Y

Diagnosis

Timing

Thrombocytopenia

Thrombosis

Alternate Causes

Timing

In a patient exposed to heparin for the first

time in 100 days, HIT begins after 4-14 days

of heparin use

A rapid fall in platelets soon after heparin is

unlikely to be HIT

Thrombocytopenia

<150K

50% fall from peak

It is uncommon for HIT to cause “single

digit” thrombocytopenia

Thrombosis

Even after stopping heparin 50% of

patients with HIT will clot within the

first 30 days

Odds ratio for clot w/ HIT = 37

Venous > Arterial

DVT/PE most common

“Weird” clots - - HIT more likely

Management

2 Do

2 Don’t

2 Tests

DO

Stop ALL heparin - - even flushes

Start alternative anticoagulation - -

before confirmatory tests return

Alternative Anticoagulation

Direct Thrombin

Inhibitors

Lepirudin

Not good in kidney

dysfunction

Argatroban

Really messes up

the INR

Fondaparinux

to temporize?

DON’T

Use coumadin too soon - - wait for full

platelet recovery, must have sufficient

overlap

Transfuse platelets - - along with TTP

this is a contraindicated condition for

platelet transfusions!

2 Tests

ELISA for antibody to PF4 (usually a

sendout, but the most helpful

confirmatory test)

Bilateral LE Doppler Venous

Ultrasound

(the presence of thrombosis greatly

strengthens your case)

Platelet Problems

Introduction

Platelets in health

Why we bleed

ITP

TTP

Conclusions

The Call . . .

Diagnosis?

ITP

Should not have

red cell changes

Can give platelets

Plasma exchange

not helpful

HIT

Needs the “H”!

No platelets

TTP

Schistocytes

No platelets

Needs plasma

exchange

Success?

Platelet Problems

Platelets in health

Why we bleed

ITP

TTP

HIT

Conclusions

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Hematology Emergencies: Problems with Platelets Emergencies: Problems with Platelets Christian...

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