Hematology: Platelets and Blood Coagulation Tests

150,000-450,000 cells/microliter

platelet range

platelets

non-nucleated, disk-shaped structures originating from megakaryocytes and critical in blood clot formation and regulate hemostasis

7-10 days

Thrombus formation occurs through 3 processes: platelet adhesion, platelet activation, and platelet aggregation; clot formation does not occur unless there is an injury or there are abnormal/nonfunctioning endogenous antithrombogenic and vasoactive substances present in the body. Platelet adhesion leads to activation then aggregation. Platelets remain in circulation for about _____ days and are destroyed by the spleen, liver, and bone marrow.

4-5 days

lifespan of transfused platelets

1. severe exercise

2. cachexia

3. polycythemia vera

4. hemolytic anemia

5. acute hemorrhage

6. chronic myelogenous leukemia

7. suppurative infection

8. status post (S/P) surgical operations

9. S/P splenectomy

10. S/P fractures (neck and femur)

11. asphyxia

platelets are elevated in

1. idiopathic thrombocytopenic purpura (ITP)

2. acute and chronic leukemias

3. hemolytic anemia

4. septicemia, typhoid fever, bacterial endocarditis

5. heparin

platelets are decreased in

thrombocytosis

elevated platelet counts (>450,000 cells/mcL) in the blood; associated with infections, malignancies, splenectomy, inflammatory disorders (RA), polycythemia vera, stress, surgery or trauma, thrombosis, ecchymosis, epistaxis, hemorrhage, cirrhosis, asphyxiation, PE, circulatory abnormalities, IDA, pancreatitis, TB

thrombocytopenia

low platelet counts (<150,000 cells/mcL); associated with ITP, DIC, aplastic anemia, hemolytic-uremic syndrome, viral infections, chemo, radiation, Heparin, Penicillins

Heparin-induced thrombocytopenia (HIT)

caused by antibodies formed against Heparin; IgG antibodies bind to heparin-PF4 complexes; leads to thrombosis

- patients on UFH are at a greater risk

- onset: 5-10 days following start of Heparin

- 4Ts score is used to predict probability

Thrombocytopenia

Timing of Platelet Count Fall

Thrombosis

other causes of Thrombocytopenia

what are the 4Ts used to assess HIT?

- ELISA: identifies anti-PF4/Heparin antibodies

- C-serotonin release assay (SRA): detects antibodies that induce activation

- Heparin-induced platelet activation (HIPA): detects antibodies that induce activation

list the tests used to diagnose HIT

- diagnosis is based on: antibody formation detection on assay, >30% drop in platelets, thrombosis/limb gangrene/necrotizing tissues at the site of injection, anaphylactoid reactions after IV admin.

1. Valproic acid, Carbamazepine, Phenytoin

2. Chemotherapy

3. Furosemide and thiazide diuretics

4. Abciximab

5. Amiodarone

6. gold compounds

7. NSAIDs

8. Penicillin

9. Quinidine

10. Sulfonamides, trimethoprim

11. Linezolid

12. Methimazole, PTU

medications that cause drug-induced thrombocytopenia

direct thrombin inhibitors: Argatroban, Lepirudin, Danaparoid, *Bivalirudin

*only indicated for patients at high risk of bleeding and at risk of HIT undergoing PCI

first line therapy for anticoagulation in patients with HIT

Fondaparinux

second-line to DTIs for anticoagulation in patients with HIT and first-line in patients with thrombosis not related to HIT as a bridge to Warfarin

150,000

Warfarin may be used for anticoagulation in patients with HIT but only when platelets return to at least ______.

7-11 fL

reference range for mean platelet volume (MPV)

mean platelet volume (MPV)

useful in distinguishing between hypo productive and hyper destructive causes of thrombocytopenia; not used alone for definite diagnosis of thrombocytopenia; routinely reported with CBC

- elevated in MI (predicts another infarction if elevated at 6 months post-MI), pregnancy (3rd trimester), hyperthyroidism

- low in HIV and hypersplenism

true

- seen in sepsis, respiratory disease, and renal failure

T/F: the lower the platelet count the higher the MPV

PT and INR

which coagulation tests are monitored while patients are on Warfarin?

aPTT and ACT

which coagulation tests are monitored while patients are on Heparin?

1. CYP2C92 and 3: decrease clearance of Warfarin S enantiomer

- decrease the maintenance dose of Warfarin in these patients

2. VKORC1: AA seen in Asians, GG genotype seen in African Americans

- not associated with increased bleeding

3. CYP4F2: affects dosing to a lesser extent; not associated with increased bleeding

genes that can affect Warfarin pharmacokinetics and pharmacodynamics

10-13 s

normal prothrombin time (PT)

prothrombin time (PT)

used to monitor Warfarin therapy; should be 2-2.5 baseline with adequate therapy

- sensitive to changes in factors II, VII, and X (more sensitive to factor VII)

- thromboplastin and calcium are added to plasma sample and the time to clot is measured

- may be elevated with PCN and cephalosporin therapy, liver disease, vitamin K deficiency, and extrinsic and common pathway clotting factor abnormalities

2-3

The desired range of INR is based on indication of anticoagulation therapy. What is the range for Afib, DVT and PE treatment, DVT prophylaxis, and valvular heart disease

2.5-3.5

The desired range of INR is based on indication of anticoagulation therapy. What is the range for mechanical prosthetic valve and recurrent thromboembolic states

risk of clotting

- requires a dose increase of Warfarin

INR below the desired range represents subtherapy and puts the patient at risk for

risk of bleeding

- readjust dosage regimen of Warfarin

INR above the desired range puts patients at risk for

1 mg/min

IV rate of vitamin K for Warfarin reversal should not exceed ___ mg/min

1 week

use of high vitamin K doses (10-15 mg) may cause Warfarin resistance for _____

22-38 s

normal range of activated partial thromboplastin time (aPTT)

activated partial thromboplastin time (aPTT)

- hereditary factors that affect aPTT: deficiency in factor II, V, VIII, IX, X, XI, XII, fibrinogen

- acquired factors that affect aPTT: Lupus, liver disease, vit. K deficiency, DIC, malnutrition, malabsorption; Heparin, lepirudin, bivalirudin, argatroban, warfarin, inhibition of factor II, V, X, or fibrinogen

primarily used to monitor Heparin therapy; should be 1.5-2.5x the baseline level for patients on Heparin

- sample should be collected 4-6 hours after start of IV infusion of Heparin

- sensitive to changes in factors IIa, IXa, and Xa

anti-Xa levels

which levels are used to routinely measure LMWH therapy?

70-180 s

reference range for activated clotting time (ACT)

activated clotting time (ACT)

mainly used to monitor heparin therapy and DTIs when high doses are required during invasive procedures; also used to monitor neutralization of heparin by protamine sulfate

- linear to increasing doses of heparin

0.3-0.7 units/mL

normal anti-Xa for Heparin

0.5-1 units/mL

normal anti-Xa for twice daily dosing of LMWH

1-2 units/mL

normal anti-Xa for once daily dosing of LMWH

anti-Xa

used to monitor therapy with LMWH but not routinely; performed in patients with renal failure, pregnancy, and obesity

- draw levels 4 hours after starting LMWH

17-25 s

normal thrombin time (TT)

thrombin time (TT)

measures the time it takes for a sample to clot after the addition of thrombin; value is compared to normal plasma control

- affected in the final phase of the common pathway and the conversion of fibrinogen to fibrin