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How To Treat Low Platelet Count Naturally

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Thrombocytopenia (Pit count < 150.000 nl)

Thrombocytopenia and Risk of Bleeding

Platelet count (cells |il)



No 1 risk


Risk with major trauma; can proceed with general surgery


Risk with minor trauma or surgery


Risk of spontaneous bleeding (less so with ITP)


Risk of severe, life-threatening bleeding


• I production hypocellular bone marrow: aplastic anemia (see "Aplastic anemia"), drugs (eg.

thiazides, antibiotics), and alcohol cellular bone marrow: MDS, leukemia, severe megaloblastic anemia marrow replacement myelofibrosis, hematologic and solid malignancies, granulomas

• t destruction immune-mediated Primary (idiopathic): immune thrombocytopenic purpura (ITP. see below) Secondary: infections (HIV. herpes viruses. HCV). collagen vascular diseases (SLE). antiphospholipid syndrome, lymphoproliferative disorders (CLL. lymphoma), drugs (many, including heparin, abciximab. quinidine, sulfonamides, vancomycin), alloimmune (posttransfusion) non-immune-mediated: MAH A (DIC. HUS.TTP), ticlopidine clopidogrel, vasculitis, preeclampsia HELLP syndrome, cardiopulmonary bypass. CWH. IABP. cavernous hemangioma

• Abnormal distribution or pooling: splenic sequestration, dilutional. hypothermia

• Unknown: Ehrlichiosis. Babesiosis. RMSF

Diagnostic evaluation

• H&P: meds. infxns. underlying conditions, splenomegaly, lymph nodes, bleeding

• CBC with differential: isolated thrombocytopenia vs. multilineage involvement

• Peripheral smear

T destruction — look for large platelets, schistocytes i production -» rarely limited to platelets look for blasts, hypersegmented PMNs.

leukoerythroblastic As rule out pseudothrombocytopenia due to platelet clumping (/ platelet count in non-EDTA-containing tube, eg citrate-containing yellow top tube)

Figure S-4 Approach to thrombocytopenia


isolated thrombocytopenia \

otherwise normal CBC & smear autoimmune diseases9 modications? infections? i—

G culprits ©culprits t \

ITP 2 immune medications infections abnormal CBC and'or smear spherocytes \

Evan's synd. hyporsplonism schistocytes


pancytopenia leuko-and'or blasts erythroblastic i + aplastic anemia myelophthisis MDS leukemia

Additional laboratory evaluations as indicated if anemia: ✓ reticulocyte count. LDH. haptoglobin, bilirubin to detect hemolysis if hemolytic anemia: ✓ PT, PTT, fibrinogen. D-dimer. Coombs. ANA BM bx for unexplained thrombocytopenia, esp. if associated with splenomegaly

Immune thrombocytopenic purpura (ITP)

• ITP refers to primary immune platelet destruction; a diagnosis of exclusion

• Clinical manifestations: insidious onset of mucocutaneous bleeding; female:male ^ 3:1

• Diagnosis of exclusion: rule out other etiologies

CBC: isolated i platelets; 10% have ITP + AIHA Evans syndrome peripheral smear: large platelets

BM bx: T megakaryocytes; perform in adults >60 y to r o myelodysplasia consider ANA, viral serologies (eg HIV, EBV. hepatitis). H. pylori Ab antiplatelet antibody tests are not useful

• Treatment: 50-75% respond to steroids, but <20% have sustained remission after taper

- 65% have long-term remission with splenectomy pits for bleeding or ? if pit <20.000 pJ; limited benefit w o concurrent IVIg or anti-Rh(D)

Treatment of ITP in Adults




1-15 mg kg d PO tapered over wks vs. dexamethasone 40 mg PO x 4 d)

Useful acutely, but long-term s e i Fc receptor on M* i anti-pit Ab production


Anti-Rh(D) lg 75 jig kg d IV

Ab-coated RBCs overwhelm M« Fc receptors

IVIg (1 g kg d IV x 2-3 d)

If pits - 5000 despite steroids Blocks Fc receptors on Mi. i anti-pit Ab production


i pit clearance

Rituximab (anti-CD20)

I pit clearance. Ab against B-cell


Danazol. vincristine

i pit clearance

Azathioprine. cyclophosphamide

I mmunosuppressants i anti-pit Ab production

AMG531.AKR-501. eltrombopag

Thrombopoiesis stim. proteins

Aminocaproic acid

Inhibits pbsmin activation


Methylprednisolone 1 g d IV x 3 d

See above


See above

Chronic Refractory

Autologous HSCT


(NtyM 2002:346:995 & 2003:349:831 & 2006:355:1672)

Overview of Heparin-induced Thrombocytopenias


Type 1

Type II


Direct effect of heparin

Immune (Ab)-mediated

IgG vs. platelet factor 4 - heparin complex





After 1-4 d of heparin therapy

After 4-10 d; but can occur early (<24 h) with h o prior exposure w in last 100 d (felt to be secondary to persistent Ab). Can occur after heparin d c.

Platelet nadir

100.000 nl

30-70.000 pJ.i >50%



Thrombotic events (HITT) in 30-50% Rare hemorrhagic complications


Can continue heparin and observe

Discontinue heparin

Alternative anticoagulation

(JACC 1998:31:1449; NEJM 2001:344:1286)

(JACC 1998:31:1449; NEJM 2001:344:1286)

• Pathophysiology (type II): Ab binds heparin-PF4 — immune complex binds to platelets platelet activation, further PF4 release -* platelet aggregates removed from circulation — thrombocytopenia; procoagubnts released by platelets and tissue factor released by endothelial cells damaged by HITAbs — prothrombotic state

• Diagnosis: need to meet clinical and pathologic criteria

Clinical: pit < 100.000 or 1 50% from baseline; or venous (DVT. PE) or arterial (limb ischemia. CVA. Ml) thrombosis (4:1 ratio); or heparin-induced skin lesions (may also manifest T heparin resistance) Pathologic: © HIT Ab using PF4-heparin EUSA ( 90% Se. re/ if high suspicion), may be confirmed by a functional platelet aggregation (serotonin-release) assay (>90% Sp)

discontinue heparin (including flushes, LMWH prophylaxis, heponn-impregnoted lines) avoid pit transfusions

• thrombosis: alternative anticoag. (lepirudin or argatroban). overlap w warfarin

(✓ chromogenic Xa to titrate), treat for -3 mos 0 thrombosis: consider screening for DVT; nonheparin anticoag. at least until pit count nl; no consensus on duration of subsequent anticoag. (likely 1 mo if no clot)

• Use of heparin if h o HIT: if disappearance of PR Ab (usually -100 d after dx). risk of HIT

recurrence low (ME/e 2001:344:1286)

Hemolytic-uremic syndrome (HUS) & thrombotic thrombocytopenic purpura (TTP)

• Definition: vascular occlusive disorders w systemic (TTP) or intrarenal (HUS) pit aggreg.

— thrombocytopenia & mechanical injury to RBCs (MAHA) (n£jm 2002:347 589)

HUS triad thrombocytopenia • MAHA renal failure

TTP pentad thrombocytopenia • MAHA • s MS renal failure • fever

• Pathophysiology: mechanism in most HUS cases is distinct from TTP (N£/m 1998:339:1578)

HUS: Shiga toxin binds & activates renal endothelial cells & pits — intrarenal thrombi TTP:. ADAMTS13 protease activity — persistence of large wVF multimers on endothelial surface — adhesion and aggregation of passing platelets — thrombosis

• Clinical manifestations and associations

HUS: usually in children; prodrome of bloody diarrhea due to enterohemorrhagic £ coli TTP: usually in adults; idiopathic, drugs (CsA.gemcitabine. mitomycin C. tidopidine. clopidogrel, quinine). HIV. pregnancy. HSCT, autoimmune disease, familial

• Diagnosis: unexplained thrombocytopenia (typically 20k) • MAHA — sufficient for dx schistocytes. Coombs, normal PT PTT & fibrinogen Tt LDH (tissue ischemia • hemolysis).r indirect bili.. U haptoglobin. T Cr (esp. in HUS) Biopsy: arterioles filled with platelet hyaline thrombi Ddx: DIC. vasculitis, malignant hypertension, preeclampsia HELLP syndrome

• Treatment plasma exchange glucocorticoids in all adults w suspected TTP-HUS;

FFP if delay to plasma exchange;

platelet transfusions contraindicoted -* T microvascular thrombosis (N£/m 2006:354:1927) Disseminated intravascular coagulation (DIC): see "Disorders of Coagulation"

Disorders of Platelet Function

Mechanisms and Etiologies of Platelet Function Abnormalities

Function Adhesion


Uremia; acquired vWD


Granule release

Afibrinogenemia Glanzmanns thrombasthenia Chediak-Higashi syndrome Hermansky-Pudlak syndrome

Tidopidine. clopidogrel. GP lib Ilia Dysproteinemias (myeloma) Drugs (ASA NSAIDs); liver disease; MPD; cardiopulmonary bypass

Tests of platelet function

• Bleeding time: global screen of platelet function; not reliable and rarely used

• Platelet aggregation tests: measure aggregation in response to agonists (eg. ADP)

von Willebrand's disease (vWD)

• Most common inherited bleeding disorder

• von Willebrand's factor (vWF) function platelet glue & plasma carrier of factor VIII

• Classification of inherited vWD

Type 1 (autosomal dominant; 85% of cases): partial quantitative deficiency in vWF Type 2 (autosomal dominant; 15% of cases): qualitative deficiency of vWF (4 types: A defective multimers, B excessive GPIblX binding. M defective GPIblX binding. N defective factor VIII binding) Type 3 (autosomal recessive; rare): near complete deficiency of vWF

• Acquired vWD: associated with many disorders (malignancy, autoimmune, hypothyroidism.

drugs) and caused by different mechanisms (anti-vWF Abs. 1 clearance, i synthesis)

• Diagnosis: 1 vWF:Ag. I vWF activity (measured by ristocetin cofactor assay). I factor

VIII. * î PTT. 2 1 platelets; confirm with vWF multimer analysis

• Treatment: desmopressin (IV IN) r endothelial cell release of vWF; variable efficacy depending on type... / response before use w subscq. bleeding or procedures; vWF replacement: cryoprecipitate. factor VIII concentrates rich in vWF. recomb. vWF (NEJM 2004:351:683)

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