12-1: 1/5 - Platelet Disorders

Front 1

Platelet:
Life Span
Role in Primary and Secondary Hemostasis

Back 1

8-10 days (removed by RES)

Primary hemostasis: form platelet plug

Secondary hemostasis: provide surface and phospholipid for coag cascade

Front 2

Describe the four major steps of making a blood clot. Begin with damage to blood vessel.

Back 2

1) Damage to endthoelial lining-->vasoconstriction
2) Platelet adhesion and aggregation (primary hemostasis) to form plug
3) Blood coagulation (secondary hemostasis)
4) Fibrinolysis to shave off blood clot

Front 3

What defines thrombocytopenia?

Back 3

Platelet count less than 150,000/mm3

Front 4

What would you expect to see in a patient with a platelet count <20,000?

Back 4

Spontaneous bruising
Minor bleeding
Petechiae
Severe spontaneous bleeding possible

Front 5

What would you expect to see in a patient with a platelet count <10,000?

Back 5

Severe spontaneous bleeding

Front 6

Bleeding pattern for primary hemostasis defect.

Back 6

Microhemorrhage--petechiae; if coalesce-->purpura

May lead to easy bleeding after brushing teeth (gingival bleeding), menorrhagia

Front 7

Causes of thrombocytopenia.

Back 7

-Dec'd production
-Inc'd destruction
-Splenomegaly
-Pseudothrombocytopenia (clumping)

Front 8

Causes of decreased production of thrombocytopenia.

Back 8

Post-viral infection (rubella, mumps, varicella, EBV, parvo, hepatitis, HIV)
Chemo/XRT
EtOH
B12 or folate deficiency
BM infiltrative dz (CaP, BrCa, lymphoma, myeolma, leukemia)

Front 9

Isolated Thrombocytopenia:
General
Pathophys
Natural history

Back 9

Thrombocytopenia with normal WBC, Hgb, and smear exams and no other assocd conds that may cause thrombocytopenia.

Diagnosis of exclusion!

Pathophys: platelet destructioon and/or inhibition of platelet production by patient B lymphocytes (immune system).

Natural Hx: Resolves in children within 6 mos (no specific tx); spontaneous remission is rare in adults; usually chronically low, waxing and waning platelet count.

Front 10

Platelets are formed from ______.

Back 10

Megakaryocytes

Front 11

Isolated thrombocytopenia:
Who should be treated?
Treatments

Back 11

Should only treat patients with moderate or severe thrombocytopenia; major hemorrhage (i.e., intracranial) rare, but possible.

-Prednisone to suppress immune system
-IV IgG: Fc portion of molecule binds receptors on RES displacing Ab covered platelets (lasts ~3 weeks, 75% response rate; good for surgery prep)

-Anti-D Ab: Ab to RBC antigen (similar to Rhogam)

Front 12

Rituximab:
Use
MOA

Back 12

Second line treatment for Isolated Thrombocytopenia

-Monoclonal Ab to B cells (lymphocytes making plasma cells that are making Ab's against platelets)

Front 13

Romiplostim:
Use
MOA

Back 13

2nd line treatment for isolated thrombocytopenia

Thrombopoietin receptor agonist

Front 14

Eltrombopag:
Use
MOA

Back 14

2nd line treatment for isolated thrombocytopenia

Thrombopoietin receptor agonist

Front 15

Drug-Induced Thrombocytopenia:
Direct Toxicity Causes

Back 15

Chemotx
EtOH
Thiazides (mild)

Front 16

Drug-Induced Thrombocytopenia:
Hapten Mediated Causes

Back 16

Drug binds platelet-->Ab binds complex-->platelets destroyed

Heparin induced thrombocytopenia
Abciximab (IIB/IIIa inhibitor0

Front 17

Drug-Induced Thrombocytopenia:
Innocent Bystander Immune Reactions Causes

Back 17

Ab-binds drug->activates complement-->damages platelet

Ex: Quinidine

Front 18

Treatment for drug-induced thrombocytopenia.

Back 18

STOP DRUG

Front 19

Common drugs inducing thrombocytopenia.

Back 19

Abx:
Bactrim
Vanco
PCN
Acyclovir (antivirals0

H2 Blockers--pepcid (zantac)

Quinidine, tonic water

Front 20

Heparin-Induced Thrombocytopenia:
Type I vs Type II

Back 20

Type I: 2-4 days after exposure to heparin; initial slight decrease in platelets then increases w/continuation of drug; BENIGN

Type II: occurs 4-10 days post exposure; rapid dec in platelets by 50%; assocd w/thrombosis (due to platelet activation) NOT bleeding

Front 21

Heparin-Induced Thrombocytopenia Type II:
Pathophys

Back 21

IgG and IgM Abs made to heparin/platelet factor IV complex

Fc portion of Ab binds platelet, activates platelets, which release Factor IV and contributes to positive feedback loop

Platelet activtn-->thrombosis

Front 22

HIT Type II:
Diagnosis
Treatment

Back 22

Serotonin-release assay

Tx:
STOP all heparin products
Immediate anticoag w/non-heparin agent (argatroban)
-HOLD coumadin until adequately anticoag'd and platelets >100,00
-NO PLATELET transfusions (this is a platelet activtn state)

Front 23

Thrombotic Thrombocytopenic Purpura:
Pathophys

Back 23

Lack of ADAMTS13 protein-->less cleaving of VWF
-->Large VWF on vascular endothelial cells-->endothelial damage, fibrin formation, microvessel THROMBI-->multi-organ failure

Front 24

Thrombotic Thrombocytopenic Purpura:
Clinical Pentad
Treatment

Back 24

Thrombocytopenia***
Microangiopathic Hemolytic Anemia (schistocytes)***
Fever
Neurologic Syx
Renal Failure

Only need starred items to make diagnosis.

Tx:
Plasma exchange!!!! Gets rid of Ab and high molecular VWF, provides cleaving protease

Front 25

Platelet Dysfunction:
Acquired Causes

Back 25

Liver Dz
Renal Dz (uremia)
Cardiopulmonary bypass

Inherited dysfn is rare

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