Thrombocytopenia and ITP

Today we discussed an approach to a bleeding diathesis, and issues related to thrombocytopenia and ITP. A few key points:

General approach to bleeding history:
Try to differentiate primary hemostasis problem (vascular response and platelet plug) vs. secondary hemostasis problem (fibrin clot, or resolution phases)

Clues:
Primary- excessive immediate post-traumatic bleeding usually. Petechiae, purpura, mucosal bleeds: nose, mouth, gums, GI, uterine
Secondary- delayed, subcutaneous, deep tissues, joints, GI/GU, post-op.
Acquired vs. inherited: new-onset vs. lifelong, new medical problem or drug, FHx.


General approach to thrombocytopenia

3 major categories
1. Decreased platelet production
2. Increased platelet destruction or platelet consumption
3. Sequestration

Decreased PLT production: Bone marrow problem; marrow shows decreased megakaryocytes
Aplastic anemias (congenital or acquired)
Myelophthisic anemia - i.e. marrow replacement (malignancy, granulomatous, etc)
Megaloblastic anemias (B12, folate deficiency)
Marrow suppression from drugs, toxins, infection, etc)

Peripheral destruction or consumption
Immune-mediated: ITP- Primary (idiopathic) or secondary (SLE, HIV, EBV B-cell disorders), drug-induced, post-transfusion
Non-immune: Thrombotic thrombocytopenia purpura- TTP, disseminated intravascular clotting

Sequestration:
Usually portal hypertension, hypersplenism

ITP specifics

Most cases are idiopathic.
In adults, it is generally chronic, the onset is often insidious. Approximately
twice as many women as men are affected

If all these conditions are met, bone marrow bx (gold standard) is not required
-age less than 60
-isolated TCP
-no splenomegaly
-no lymphadenopathy

To exclude before calling "idiopathic ITP":
-non-immune causes of TCP (primary marrow problem, TTP, HIT, DIC, etc)
-infection- HIV especially, EBV
-inflammatory disorders, esp. SLE
-malignancy, esp. B-cell disorders (CLL, myeloma, etc)
-drug induced (for immune-mediated, B-lactams, quinine, vancomycin, others)

Therapy:
In serious bleeding
1) hemodynamic and RBC transfusion support
2) platelet transfusion
3) steroid
4) IVIG
5) some evidence for factor VII in life-threatening bleeding

Most pts require therapy; those who do not are those with mild (over around 50), asymptomatic, incidentally discovered thrombocytopenia. Otherwise, options are:
-Steroids (prednisone 1mg/kg, tapered over 4-6 weeks depending on response or dexamethasone 40mg PO x 4d). 50% have relapse. RCT underway comparing these regimens
-IVIG; indicated for severe bleeding, pre-operatively or pre-delivery, and in steroid-refractory cases
-Splenectomy (need appropriate vaccinations first)
-Rituximab (controversial whether should be tried before splenectomy)

In chronic refractory cases, there may be a role for vincristine, azathioprine and cyclophosphamide, and thrombopoeitin agonists

Links:
Click here for a NEJM review of ITP

Click here for a series demonstrating effect of short course of dexamethasone described above

Thrombocytopenia: an approach

(a megakaryocyte pictured on the left)

Look for mucocutaneous bleeding: gingival bleeding after brushing teeth, epistaxis, menorrhagia, metrorrhagia, and easy bruising. Also look for petichiae (non-palpable, non-blanchable) in dependent areas, like the shins and feet. These should not be on the soles of the feet as there is a thick protective layer of subcutaneous tissue. You may see them on the palate as well. Check out the photos at the bottom.

Decreased Production of platelets:

• Hypocellular bone marrow: from aplastic anemia of which there are many causes(idiopathic, radiation, chemo, medications, viruses). Other cell lines will also be decreased.


• Cellular bone marrow: myelodysplastic syndromes, leukemia


• Replacement of marrow: with primary or secondary malignancies, myelofibrosis, or granuloma (eg. TB, sarcoid).

you can read more about related issues here.

Increased Destruction of platelets:

• Immune mediated: Idiopathic Throbocytopenia Purpura (primary), or secondary to Collagen Vascular Diseases (eg. SLE), Infections (eg. HIV, Hep C), Drugs (eg. heparin, sulfa), Lymphoproliferative diseases (CLL, lymphoma), and the Antiphospholipid Antibody Syndrome.


• Non-Immune mediated: Think about things like Disseminated Intravascular Coagulation, Thrombotic Thrombocytopenia Purpura and it's cousin the Hemolytic Uremic Syndrome, HELLP syndrome in pre-eclampsia, and malignant hypertension.

Sequestration:

• Mostly in a large spleen.

Other:

• Very rarely, blood collected in the tube will react to a chemical (EDTA) and cause platelet clumping - this may cause 'spurious' thrombocytopenia. The platelets work just fine, they just react to the EDTA.

(petichiae to the left, and palatal petichia + gingival bleeding below)