Thrombocytopenia.

For the benefit of busy general practitioners who are likely to encounter thrombocytopenia in everyday practice, Sekhon and Roy, (1) in this issue of the Journal, have provided a review of causes and a practical approach to the management of thrombocytopenia in adults.

The principal goal in the management of thrombocytopenia is prevention of death from bleeding. Before embarking on a costly search for thrombocytopenia, it is important to rule out the following: 1) pseudothrombocytopenia caused by platelet clumping by examination of a peripheral blood smear, (2) dilutional thrombocytopenia from massive blood loss and transfusional support with packed RBCs, (2,3) and 3) mild to moderate thrombocytopenia associated with pregnancy in a healthy woman. (4,5)

The causes of pregnancy-associated thrombocytopenia, which may affect up to 10% of pregnancies, range from benign conditions such as gestational thrombocytopenia to syndromes associated with significant morbidity. Gestational thrombocytopenia accounts for over 75% of all cases of pregnancy-associated thrombocytopenia. (4) The etiology of this disorder is unknown, but may be due to the effect of hemodilution or accelerated platelet clearance through immune or nonimmune mechanisms. (4) It is clinically unimportant, unless the platelet count is below 70,000/[micro]L and there is concern regarding the safety of epidural anesthesia. It usually resolves spontaneously following delivery. Immune thrombocytopenia (ITP) accounts for 5% of pregnancy-associated thrombocytopenias and may affect the fetus or the newborn. Pregnancy-related syndromes such as pre-eclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets), or DIC (disseminated intravascular coagulation) caused by abruptio placentae are serious conditions requiring active intervention. About 50% of patients with pre-eclampsia develop thrombocytopenia, with severity proportional to underlying disease. Even though these syndromes typically resolve following delivery, careful follow-up is necessary to exclude other disorders such as thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS). (4)

TTP/HUS, and more importantly, heparin-induced thrombocytopenia (HIT) are serious conditions requiring urgent intervention and hematologic consultation. The importance of HIT cannot be overemphasized and is one of the most under recognized causes of thrombocytopenia with severe complications. HIT should be considered in any patient who develops new thrombosis or an extension of existing thrombus despite adequate treatment with unfractionated or low-molecular-weight heparin in association with decreasing platelet counts, even in the normal range. Consultation with a hematologist and treatment with lepirudin or argatroban should not be delayed, even if laboratory confirmation for antiplatelet-4 antibody is not available immediately. (6)

Thrombocytopenia among patients hospitalized in medical or surgical ICUs is often multifactorial. An extensive evaluation may not be particularly helpful as infection and sepsis is found to be the ultimate cause in most cases. The major cause of platelet destruction in sepsis is possibly due to hemophagocytosis associated with high macrophage-colony stimulating factor concentrations. (7-10) Thrombocytopenia in ICU patients is a critical prognostic indicator and thrombocytopenic patients are shown to have higher mortality rates and longer hospital stays. (11-13) One study revealed that a 30% decrease in platelet counts was a significant risk factor for ICU death. (14)

Patients with moderate thrombocytopenia probably should not participate in extreme athletics such as boxing, football, and karate. However, no restrictions are necessary for usual activities. Patients should be advised against competitive contact sports, horseback riding, and skiing, Patients with platelet counts less than 50,000 should not be placed on aspirin therapy, as the bleeding time is already prolonged in patients with thrombocytopenia.

References

1. Sekhon S, Roy V. Thrombocytopenia in adults: a practical approach to evaluation and management. South Med J 2006;99: 491-498.

2. Leslie SD, Toy PT. Laboratory hemostatic abnormalities in massively transfused patients given red blood cells and crystalloid. Am J Clin Pathol 1991;96:770-773.

3. Counts RB, Haisch C, Simon TL, et al. Hemostasis in massively transfused trauma patients. Ann Surg 1979;190:91-99.

4. McCrae KR, Bussel JB, Mannucci PM, et al. Platelets: an update on diagnosis and management of thrombocytopenic disorders. Hematology 2001:282-305.

5. Tefferi A, Hanson CA, Inwards DJ. How to interpret and pursue an abnormal complete blood cell count in adults. Mayo Clin Proc 2005;80:923-936.

6. Daneschvar HL, Daw H. How to interpret and pursue an abnormal complete blood cell counts in adults. Mayo Clin Proc 2005;80:1389-1392.

7. Stephan F, Montblanc J, Cheffi A, et al. Thrombocytopenia in critically ill surgical patients: a case-control study evaluating attributable mortality and transfusion requirements. Crit Care 1999;3:151-158.

8. George JN. Platelets. Lancet 2000;355:1531-1539.

9. Stephan F, Thioliere B, Verdy E, et al. Role of hemophagocytic histiocytosis in the etiology of thrombocytopenia in patients with sepsis syndrome or septic shock. Clin Infect Dis 1997;25:1159-1164.

10. Francois B, Trimoreau F, Vignon P, et al. Thrombocytopenia in the sepsis syndrome: role of hemophagocytosis and macrophage colony-stimulating factor. Am J Med 1997;103:114-120.

11. Stephan F, Hollande J, Richard O, et al. Thrombocytopenia in a surgical ICU. Chest 1999;115:1363-1370.

12. Vanderschueren S, de Weerdt A, Malbrain M, et al. Thrombocytopenia and prognosis intensive care. Crit Care Med 2000;28:1871-1876.

13. Baughman RP, Lower EE, Flessa HC, et al. Thrombocytopenia in the intensive care unit. Chest 1993;104:1243-1247.

14. Strauss R, Wehler M, Mehler K, et al. Thrombocytopenia in patients in the medical intensive care unit: bleeding prevalence, transfusion requirements, and outcome. Crit Care Med 2002;30:1765-1771.

Live each season as it passes; breathe the air, drink the drink, taste
the fruit, and resign yourself to the influences of each.
--Henry David Thoreau

Ashok K. Malani, MD, MS, FRCS 

From St. Joseph Oncology, St. Joseph, MO.

Reprint requests to Ashok K. Malani, MD, MS, FRCS, 902 North Riverside Road, Suite #200, St. Joseph, MO 64507. Email: [e-mail]

Accepted January 12, 2005.