Thrombocytopenia Caused by Platelet Destruction, Hypersplenism, or Hemodilution

Table 57-1 Mechanisms of Platelet Destruction or Consumption

CPB, Cardiopulmonary bypass surgery; DIC, disseminated intravascular coagulation; HIT, heparin-induced thrombocytopenia; HUS, hemolytic uremic syndrome; IgG, immunoglobulin G; ITP, Idiopathic (immune) thrombocytopenic purpura; NAIT, Neonatal alloimmune thrombocytopenia; PAT, passive alloimmune thrombocytopenia; PE, pulmonary embolism; PTP, posttransfusion purpura; RES, reticuloendothelial system; TTP, thrombotic thrombocytopenic purpura; vWF, von Willebrand factor.

* See Chapter 56 for a discussion of thrombocytopenia in these disorders.

† Although platelet destruction is not directly caused by antibodies, immune mechanisms can explain altered vWF (e.g., autoimmune clearance of vWF-cleaving metalloprotease).

Figure 57-1 POSTSURGERY PLATELET COUNT CHANGES.

Initial platelet count declines result from hemodilution and increased platelet consumption, with the platelet count nadir occurring between days 1 to 4 (median, day 2). There is constitutive production of thrombopoietin (TPO) by the liver. TPO binds to platelets and megakaryocytes via a specific receptor (c-Mpl, not shown), and receptor-bound TPO is removed from circulation and degraded. The level of circulating TPO is thus inversely related to the mass of platelets and megakaryocytes. In early postsurgery thrombocytopenia, fewer TPO binding sites are available, resulting in high free TPO levels, which stimulates megakaryocyte proliferation and differentiation and leads to increased platelet production. With subsequent thrombocytosis, the high platelet mass acts as a “sink” for removing TPO, with decreased stimulus for platelet production. Thus, after acute postsurgery thrombocytopenia, TPO levels rise about twofold, leading to increased platelet production that begins on days 2 to 4, with resulting thrombocytosis that generally peaks at approximately day 14 (postoperative thrombocytosis) and returns to baseline by about day 21.

(Reprinted, with modifications, with permission, from Arnold DM, Warkentin TE: Thrombocytopenia and thrombocytosis. In Wilson WC, Grande CM, Hoyt DB, editors: Trauma: Critical care, vol 2. New York, 2007, Informa Healthcare, p 983.)

Figure 57-2 TIMING OF ONSET AND SEVERITY OF THROMBOCYTOPENIA: IMPLICATIONS FOR DIFFERENTIAL DIAGNOSIS.

The usual postoperative platelet count nadir is seen between postoperative days 1 to 3 (inclusive). Early and progressive platelet count declines often reflect severe postoperative complications such as sepsis and multiorgan failure; severe thrombocytopenia can (rarely) indicate postsurgery thrombotic thrombocytopenic purpura (TTP). Thrombocytopenic disorders that begin approximately 1 week after surgery are often immune mediated: moderate thrombocytopenia can indicate heparin-induced thrombocytopenia (HIT), both “typical onset” or (if heparin is not being given) “delayed onset”; very severe thrombocytopenia can indicate drug-induced immune thrombocytopenic purpura (D-ITP) or (rarely) posttransfusion purpura (PTP). An abrupt decline in platelet count after receiving a heparin bolus in a patient who has received heparin within the past 7 to 100 days can indicate “rapid-onset” HIT; thrombocytopenia that begins abruptly after transfusion of a blood product can indicate sepsis from bacterial contamination or (rarely) passive alloimmune thrombocytopenia (PAT) caused by transfusion of platelet-reactive alloantibodies.

(Reprinted, with permission, from Greinacher A, Warkentin TE: Acquired non-immune thrombocytopenia. In: Marder VJ, Aird WC, Bennett JS, et al, editors: Hemostasis and thrombosis: Basic principles and clinical practice, ed 6. Philadelphia, 2012, Lippincott Williams & Wilkins, in press.)

Table 57-3 Laboratory Tests Used to Investigate a Patient With Thrombocytopenia

ANA, Antinuclear antibody; aPL, antiphospholipid; aPTT, activated partial thromboplastin time; CBC, complete blood count; DIC, disseminated intravascular coagulation; D-ITP, drug-induced immune thrombocytopenia; ELISA, enzyme-linked immunosorbent assay; GP,