Page 2221 - Hematology_ Basic Principles and Practice ( PDFDrive )

1968 Part XII Hemostasis and Thrombosis

TABLE Mechanisms for Thrombocytopenia Complicating immune complexes containing IgM antiidiotype antibodies (which
132.6 Infections could explain the paradox of high levels of platelet-associated IgG and
IgM with low serum levels of platelet-reactive antibodies). Anti-HIV
Mechanism for Thrombocytopenia Selected Example(s) a therapy (e.g., zidovudine, HAART) often raises the platelet count
Increased Platelet Destruction in patients with HIV-associated thrombocytopenia. Most patients
DIC Meningococcemia with HIV-associated thrombocytopenia respond to conventional
treatments for ITP, including corticosteroids, splenectomy, IVIg, and,
Hemophagocytosis Septicemia, EBV infection particularly, anti-D.
Platelet-reactive autoantibodies Varicella, subacute bacterial
(acute) endocarditis (rare)
Platelet-reactive autoantibodies HIV infection Systemic Lupus Erythematosus
(chronic)
Immune-mediated thrombocytopenia, which occurs in as many as
HUS Verocytotoxin-producing 25% of patients with SLE, is associated with a twofold increased risk
Escherichia coli, Shigella spp., of organ damage events. Many different types of platelet–IgG interac-
HIV infection
tions are described (e.g., antiglycoprotein, antiglycolipid, β 2-
Antibodies against platelet- Malaria glycoprotein I [β 2 GPI]–containing immune complexes). In addition,
adsorbed microbial antigens antithrombopoietin, anti–c-Mpl (thrombopoietin receptor), and
Hypersplenism anti-CD40 ligand autoantibodies have been reported. Multiple causes
Acute Disseminated Mycobacterium for thrombocytopenia—increased platelet destruction, hypersplen-
avium infection in HIV ism, and even impaired platelet production related to antibody-
infection induced megakaryocytic hypoplasia—have been reported. The
Chronic Viral chronic active hepatitis, predominant explanation for thrombocytopenia in SLE remains
malaria unknown.
Several thrombocytopenic syndromes are seen in patients with
Decreased Platelet Production SLE. For many patients, the thrombocytopenia is chronic, resembling
Replacement of BM by Ehrlichiosis, tuberculosis ITP, and is the predominant clinical manifestation of the lupus.
granulomas
Often, these patients have a prolonged bleeding time despite mild
Infection of megakaryocytes HIV infection thrombocytopenia. Some thrombocytopenic patients with SLE have
Transient virus-induced aplasia Parvovirus B19 infection antiphospholipid (aPL) antibodies and are at increased risk for
(erythroblastopenia thrombotic rather than bleeding complications (see Chapter 141).
predominates) Acute, severe thrombocytopenia can be a prominent feature in
Multiple Mechanisms patients with a severe multisystem exacerbation of lupus. Rarely,
Platelet destruction plus Recurrent malaria patients with SLE develop an illness that closely resembles TTP or
hypersplenism HUS; these patients should be treated with plasma exchange. Throm-
bocytopenia as a feature of SLE-associated, viral-induced macrophage
Increased platelet destruction, Chronic HIV infection activation syndrome has been reported.
decreased platelet production, Treatment of the thrombocytopenia of SLE is similar to that of
hypersplenism ITP (see Chapter 131). Corticosteroids constitute the first line of
a References can be found in Hoffman R, Benz EJ Jr, Shattil SJ, et al, eds: therapy, but many patients do not respond or require high doses.
Hematology: Basic Principles and Practice, ed 3. New York, 2000, Churchill High-dose IVIg may be useful in patients who are bleeding to tran-
Livingstone. BM, Bone marrow; DIC, disseminated intravascular coagulation; siently increase the platelet count. Before resorting to splenectomy,
EBV, Epstein-Barr virus; HIV, human immunodeficiency virus; HUS, hemolytic
uremic syndrome. one could try danazol (an attenuated androgen) in doses of
200–800 mg/day. Higher doses can cause hepatitis. Typically, several
weeks of treatment are required before a benefit is seen. Splenectomy
is probably as effective in achieving platelet count remission in SLE
as in ITP. Patients with refractory thrombocytopenia sometimes
(e.g., concomitant coagulopathy, an invasive procedure, uremic benefit from more aggressive therapies, such as azathioprine,
platelet dysfunction). The use of heparin for patients with septic intermittent-pulse cyclophosphamide, plasmapheresis synchronized
shock and DIC is controversial. However, heparin may be of benefit with pulse cyclophosphamide, cyclosporine, thrombopoietin mimet-
in patients with clinical evidence of DIC and microvascular throm- ics, or rituximab.
bosis (e.g., acral tissue ischemia or necrosis). The possibility of
acquired protein C deficiency complicating acute DIC should also
be considered in septic patients with purpura fulminans, such as that Antiphospholipid Syndrome
4,5
secondary to meningococcemia, or preceding “shock liver,” in
24
whom treatment with heparin and plasma could be beneficial. Antiphospholipid syndrome (APS; see Chapter 141) is characterized
Vitamin K administration is reasonable, although it will not help in by occurrence of one or more clinical events (e.g., venous, arterial or
the absence of vitamin K deficiency. small vessel thrombosis, pregnancy loss, preterm delivery for patients
Thrombocytopenia in patients infected with HIV poses a special with severe preeclampsia or placental insufficiency) associated with
diagnostic problem because there are many potential explanations IgG, IgM, or IgA antibodies that recognize a complex of one or more
for the thrombocytopenia. These include immune platelet destruc- protein cofactors (e.g., β 2 GPI, annexin V, prothrombin, protein C,
tion, impaired platelet production secondary to HIV infection protein S) bound to negatively charged phospholipid. Many patients
of megakaryocytes, drug-induced myelosuppression (commonly (30%–50%) with this syndrome have thrombocytopenia, which is
implicated drugs include zidovudine, ganciclovir, and TMP-SMX), typically mild and intermittent; approximately 15% have auto-
HIV-associated thrombotic microangiopathy, hypersplenism, and immune hemolysis. The APS should be considered in patients who
BM infiltration by tumor or opportunistic infections. Platelet kinetic develop idiopathic lower limb or abdominal vein (mesenteric, renal,
studies have shown a complex interaction of decreased platelet produc- adrenal) thrombosis, cerebral venous (dural sinus) thrombosis, cardiac
tion, increased platelet destruction, and splenic platelet sequestration. valvulitis, nonatheromatous arterial thrombosis (especially throm-
Immune mechanisms for platelet destruction include antibodies that botic stroke in a patient younger than 50 years of age), dermal
cross-react with GPIIb/IIIa complexes (“molecular mimicry”) and microvascular thrombosis (acrocyanosis, digital ulceration or