Mcphs Mmd Ii Thrombocytopenia, Itp, Ttp, Von Willebrand Disease

Front 1

Hemostasis is broken into what two categories?

Back 1

Primary and Secondary

Front 2

This is a form of hemostasis that has vasoconstriction and formation of platelet plug

Back 2

Primary

Front 3

This is a form of hemostasis that has the formation of fibrin through the clotting cascade

Back 3

Secondary

Front 4

Characterized by mucocutaneous bleeding with petechiae, purpura, epistaxis, GI bleed or menorrhagia.
Multiple causes include viruses, drugs, alcohol.
Usually resolves once underlying problem corrected or infection clears.
Life threatening bleeding at levels <20,000

Back 4

Thrombocytopenia

Front 5

Thombocytopenia: There is a decreased number of platelets due to what three things?

Back 5

Decreased Bone Marrow Production

Increased Splenic Sequestration

Increased destruction

Front 6

This is a reason for decreased number of platelets in thrombocytopenia characterized by:

Bone marrow biopsy shows decreased numbers megakaryocytes

Often multiple cell lines affected

Causes include malignancy, marrow aplasia or fibrosis, cytotoxic drugs, and rare congenital marrow disorders.

Back 6

Decreased bone marrow production

Front 7

This is a reason for decreased number of platelets in thrombocytopenia characterized by:

Normally 30% of platelets stored in spleen

Splenectomy leads to increased platelet count

Enlarged spleen holds more platelets leading to decreased platelet count

Splenomegaly usually associated with other underlying disease: liver disease, leukemia, lymphoma, etc.

Back 7

Increased Splenic Sequestration

Front 8

This is a reason for decreased number of platelets in thrombocytopenia characterized by:

Physical destruction by mechanical valves/vascular devices, abnormal blood vessels, fibrin thrombi.

Platelets coated with antibody and destroyed by macrophages in setting of infection, drugs or autoimmune disease.

Back 8

Increased destruction

Front 9

These are all causes of what?

Chemotherapeutic agents
Thiazide Diuretics
Quinine/Quinidine
Sulfonamides
Cephalosporins
Valproic Acid and Phenytoin
Etoh (binge drinking)
Best clue is resolution once suspect agent stopped

Back 9

Drug Induced Thrombocytopenia

Front 10

Most common drug associated thrombocytopenia
May affect 10-15% hospitalized patients treated with heparin
Usually platelet count <100,000 but >20,000.
Paradoxical thrombosis
Resolves with cessation of Heparin
Must avoid heparin and LMWH in future

Back 10

Heparin Induced Thrombocytopenia

Front 11

What do you look for in the diagnostics of Thrombocytopenia?

Back 11

Check CBC, peripheral smear looking for isolated thrombocytopenia.

“Pseudothrombocytopenia” from platelets adhering to leukocytes in EDTA anticoagulated specimen.

Patient may need bone marrow biopsy.

Front 12

Immune mediated thrombocytopenia

IgG binds to membrane glycoproteins of circulating platelets

Autoantibody coated platelets induce phagocytosis by macrophages primarily in spleen

Back 12

Immune or Idiopathic Thrombocytopenic Purpura

Front 13

Acquired
Autoimmune
Usually 2-6 yrs old
Follows viral infxn
Self-limited (wks-months)

Back 13

Acute Idiopathic Thrombocytopenic Purpura (ITP)

Front 14

Associated with a variety of viruses
CMV, rubella, Epstein-Barr, HIV,Hepatitis A, B, or C

Most typically a vague respiratory or GI illness

May be associated with recent vaccination.
Rapid destruction of platelets by auto-antibodies
T
hrombocytopenia

Purpura/petechiae

Normal bone marrow

Back 14

Immune or Idiopathic Thrombocytopenic Purpura

Front 15

How do you treat Immune or Idiopathic Thrombocytopenic Purpura

Back 15

Supportive
PRBC as indicated
Steroids
Prednisone po 1-1.5 mg/kg/day
Dexamethasone 40mg po/day x 4 days
IVIG
For plts < 5000 after few days of steroids
Platelet Transfusion
For life-threatening hemorrhage

Front 16

What is a problem that may occur if you aren't treating the underlying autoimmune disorder that may accompany chronic idiopathic/immune thrombocytopenic purpura?

Back 16

You may lose the platelets that you are infusing.

Front 17

Usually women
20-40 yrs old
Remission is Uncommon
Often accompanied by underlying autoimmune,
collagen vascular or malignant disease

Back 17

Chronic ITP

Front 18

What is the TX for chronic ITP?

Back 18

RX: Prednisone
Splenectomy
IVIG
Immunosuppresion
Danazol/ Dapsone/ vinka alkaloids
Platelet transfusions

Front 19

Diagnosis of exclusion in otherwise healthy person
Look for signs/sx of underlying disease
Exam findings: petechiae, purpura, gingival bleeding, oozing from venipuncture sites, hemorrhagic bullae (increased risk for severe bleeding)
Spleen should be non-palpable

Back 19

ITP

Front 20

What is a red flag for possible ITP in a patient?

Back 20

Huge blood blisters.

Front 21

What diagnostic tests do you use with ITP?

Back 21

CBC
Peripheral smear
HIV Testing
CT/MRI
Bone Marrow Biopsy

Front 22

Diagnostic test in ITP:

Used to look for isolated thrombocytopenia (anemia/leukopenia suggest alternate diagnosis)

Back 22

CBC

Front 23

Diagnostic test in ITP:

RBC morphology is normal. Platelet morphology generally normal. Large platelets are sign of inherited platelet disorder. Clumping platelets may be due to EDTA ---pseudothrombocytopenia.

Back 23

Peripheral blood smear

Front 24

Diagnostic test in ITP:

ANA if history suggestive.

Back 24

HIV Testing

Front 25

Diagnostic test in ITP:

if concerns for severe internal bleeding.

Back 25

CT/MRI

Front 26

Diagnostic test in ITP:

Not routinely performed but may be if atypical features, elderly (age>60), if not responding to standard treatment.

Back 26

Bone Marrow Biopsy

Front 27

Biopsy in ITP shows?

Back 27

Normal to increased numbers of megakaryocytes without other abnormalities.

Front 28

What is the goal of ITP TX?

Back 28

Increase platelet counts to safe levels

Front 29

What are the drugs of choice for the initial management of ITP (may change marrow morphology)?

Back 29

Corticosteroids

Front 30

These patients do not need treatment for ITP as disease tends to be mild and self-limited?

Back 30

Children

Front 31

ITP patients should avoid this because it will add functional defect to existing quantitative defect?

Back 31

Aspirin

Front 32

If you have a severe bleeding episode with with ITP how do you TX it?

Back 32

Use standard emergency and critical care, transfuse platelets if severe bleeding

Front 33

This is usually curative for acute ITP, less predictable for chronic ITP?

Back 33

Splenectomy

Front 34

What is something that is very important to do when treating a patient with ITP?

Back 34

Consult hematologist

Front 35

What are two agents used in the tx of ITP?

Back 35

IVIG or RhIG (in RH+ individuals with intact spleen)

Front 36

May be indicated if inadequate response to treatment after 6 months. (goal platelet count >30,000)
Carries lifetime increased risk of sepsis from encapsulated bacteria.
Make sure patients immunized against H. influenza type b, s. pneumonia, meningococcus.

Back 36

Splenectomy

Front 37

If there is a relapse of ITP after splenectomy what do you have to look for?

Back 37

Look for accessory spleen if relapse after splenectomy.

Front 38

Patients who have had a splenectomy will show what on their RBC's?

Back 38

Howell-Jolly Body

Front 39

Rare life-threatening multi-system disorder (1:50,000 hospital admissions/year)
Adults, 40’s-50’s, female:male is 2:1
Microangiopathic hemolytic anemia
Thrombocytopenia
Neurologic abnormalities
Fever
Renal dysfunction

Back 39

Thrombotic Thrombocytopenic Purpura (TTP)

Front 40

Morbidity associated with TTP is due to what?

Back 40

Morbidity associated with TTP: stroke, TIA, MI, hemorrhage.

Front 41

If this is untreated mortality approaches 90%?

Back 41

TTP

Front 42

Acute onset of symptoms
Altered mental status, seizure, hemiplegia, paresthesias, visual disturbance, aphasia
Fatigue secondary to anemia
petechiae common, severe bleeding uncommon
50% have fever
dark urine secondary to hemoglobinuria

Back 42

TTP: History

Front 43

Findings depend on organ system affected

Fever

Altered mental status, focal neurologic deficits

Organomegaly (splenomegaly) is not common

Back 43

TTP: Exam

Front 44

What are the five causes of TTP?

Back 44

Pregnancy/ postpartum (10-25% cases)

HIV/ Lymphoma
Thrombotic microangiopathic disorder

Cancer

Toxins
Escherichia coli, spider and bee venom

Drugs
sulfa drugs, cyclosporine, cocaine, ticlopidine, OCP, penicillin, rifampin, chemotherapy agents (mitomycin C, tamoxifen, bleomycin, cytosine arabinoside, daunomycin)

Front 45

What is associated with the work up of TTP?

Back 45

CBC: WBC increased or normal, Hgb decreased, Platelets 20-50K
Peripheral smear moderate to severe schistocytosis
PT/PTT normal
D-dimer usually normal, Fibrinogen high to high normal
BUN/Creatinine depends on renal involvement
LDH/Indirect Bilirubin: markedly elevated
Direct Coombs test (rule out autoimmune hemolytic anemia)
HIV testing
New testing for vWF-cleaving protease activity (not routine)
CT or MRI if stroke-like symptoms
Biopsy shows platelet rich/fibrin poor thrombi

Front 46

If there are stroke like symptoms with TTP it is important to do what?

Back 46

Make sure there is no intercranial hemorrhage.

Front 47

What is the TX for TTP?

Back 47

PLASMAPHERESIS (iv plasma exchange): inhibitory antibodies are removed and the plasma is replenished with the deficient protease

Front 48

If plasmapheresis is not immediately available for someone with TTP what do you do?

Back 48

If plasmapheresis is NOT immediately available, begin plasma infusion!!
FFP 30mL/kg

Front 49

Initiate treatment as soon as diagnosis is seriously suspected (very high mortality without treatment)
Unexplained microangiopathic hemolytic anemia without other cause justifies plasma exchange
Plasma exchange with FFP
If unavailable then infuse FFP until transfer

Back 49

TTP Treatment

Front 50

Treatment generally consists of 5 plasma exchanges in first 10 days
Response criteria: Resolution of Neuro sx, normalization of Hgb, platelets, LDH, bilirubin and creatinine
+/- corticosteroids, vincristine
Avoid platelet transfusion
Consult Hematologist, Neurologist, Nephrologist

Back 50

TTP TX/Management

Front 51

Inherited/ Congenital
Family of bleeding disorders caused by abnormal von Willebrand factor (VWF)
Most common hereditary bleeding disorder

Back 51

Von Willebrand's Disease

Front 52

What is the role of VWF in primary and secondary hemostasis?

Back 52

Primary Hemostasis: VWF links platelets to damaged subendothelium

Secondary Hemostasis (involving FVIII): VWF protects factor VIII from degradation and delivers it to site of injury

Front 53

Quantitative or qualitative abnormality of VWF, large glycoprotein that carries FVIII.

Back 53

VWD

Front 54

VWD: partial quantitative deficiency, 20-50% of normal

Back 54

VWD Type I

Front 55

VWD: Qualitative deficiency (4 subtypes)

Back 55

VWD Type II

Front 56

VWD: Total deficiency, recessive trait, causes profound bleeding disorder

Back 56

VWD Type III

Front 57

What are the things you look for in diagnosing VWD?

Back 57

Increased or easy bruising
Recurrent epistaxis
Menorrhagia
Postoperative bleeding
Family history of a bleeding diathesis

LABS:
Prolonged bleeding time & prolonged PTT
Platelet VWF analysis/ Gene analysis
Factor VIII levels - Low

Front 58

What is the TX for VWD?

Back 58

DDAVP
Factor VIII Concentrates
Crypoprecipitate
Fresh Frozen Plasma
Epsilon amino caproic acid (Amicar)

Front 59

What TX for VWD do you not use if a patient has type III VWD?

Back 59

DDAVP