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1956 Part XII Hemostasis and Thrombosis

TABLE Mechanisms of Platelet Destruction or Consumption
132.1
Type of Thrombocytopenia Specific Example(s)
Immune Mediated
Autoantibody-mediated platelet destruction by RES Primary and secondary idiopathic (immune) ITP a
a
a
Alloantibody-mediated platelet destruction by RES NAIT, PTP, PAT; alloimmune platelet transfusion refractoriness a
Drug-dependent, antibody-mediated platelet destruction by RES Drug-induced immune ITP (e.g., vancomycin) (see Fig. 132.5)
Platelet activation by binding of IgG Fc of drug-dependent IgG to platelet HIT
FcγIIa receptors
Non–Immune Mediated
a
Platelet activation by thrombin or proinflammatory cytokines DIC ; septicemia or systemic inflammatory response syndromes
Platelet destruction via ingestion by macrophages (hemophagocytosis) Infections, certain malignant lymphoproliferative disorders
Platelet destruction through platelet interactions with altered vWF b TTP, HUS a
a
Platelet losses on artificial surfaces CPB, use of intravascular catheters
a
Decreased platelet survival associated with cardiovascular diseases Congenital and acquired heart disease, cardiomyopathy, PE
a See Chapter 131 for a discussion of thrombocytopenia in these disorders.
b Although platelet destruction is not directly caused by antibodies, immune mechanisms can explain altered vWF (e.g., autoimmune clearance of vWF-cleaving
metalloprotease).
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.

1 2 3 4
Acute thrombocytopenia Increased platelet Decreased platelet
Steady state (hemodilution/increased production production
Surgery platelet consumption)

Surgery 3 4 Liver
Platelet count 1 2 (platelet count peak, day ~14) 1 Thrombopoietin
Postoperative thrombocytosis
Megakaryocyte

0 5 10 15 20 25 Platelet
Days after surgery
Fig. 132.1 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 2–4, 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: Throm-
bocytopenia and thrombocytosis. In Wilson WC, Grande CM, Hoyt DB, editors: Trauma: Critical care, vol 2, New York,
2007, Informa Healthcare, p 983).