Page 2023 - Williams Hematology ( PDFDrive )

1998 Part XII: Hemostasis and Thrombosis Chapter 117: Thrombocytopenia 1999

TABLE 117–2. Inherited Thrombocytopenia concomitant alcohol abuse (Chap. 41). One large study of 139 patients
examined the rates of cytopenias associated with megaloblastic anemia
I. Congenital hypo-/amegakaryocytic thrombocytopenias in India. In this study, 76 percent had isolated vitamin B deficiency,
61
12
A. Congenital amegakaryocytic thrombocytopenia (CAMT) 7 percent had isolated folate deficiency, 9 percent had a combined defi-
B. Congenital hypo-/amegakaryocytic thrombocytopenia ciency, and 8 percent had normal vitamin levels. All were anemic by
with skeletal abnormalities definition, and 80 percent had thrombocytopenia with mild to mod-
1. Thrombocytopenia with absent radii (TAR) syndrome erate depression of the platelet count. More than half of those with
2. Amegakaryocytic thrombocytopenia with radioulnar thrombocytopenia were also neutropenic. The authors of this study
synostosis (ATRUS) suggested that the cytopenias tended to progress from isolated anemia,
3. Fanconi anemia to anemia plus thrombocytopenia, to pancytopenia, with the degree of
cytopenia related to the severity of vitamin deficiency. Occasionally,
II. MYH9-related diseases thrombocytopenia is severe in patients with megaloblastic anemia and,
A. Macrothrombocytopenia, Döhle-like inclusion bodies in when accompanied by fever, hepatomegaly, and splenomegaly, and
leukocytes; nephritis ± hearing loss ± cataracts may suggest a diagnosis of acute leukemia. In these syndromes, the pri-
III. Platelet granule deficiencies (storage pool disease) mary mechanism of thrombocytopenia is ineffective platelet produc-
62
A. α-Granule defects tion ; marrow megakaryocyte number usually is normal or increased.
1. Gray platelet syndrome Abnormalities of megakaryocyte morphology are much less distinctive
2. Paris-Trousseau syndrome than the characteristic erythroid and myeloid defects, but often nuclear
abnormalities are seen, with nuclei of larger size and dispersed nuclear
3. Quebec platelet syndrome segments, rather than single polyploid nuclei. Thrombocytopenia
63
4. Arthrogryposis–renal dysfunction–cholestasis (ARC) may be seen in association with vitamin B deficiency when the lat-
12
syndrome ter results from autoantibodies against parietal cells or intrinsic factor
B. Dense granule defects: and is associated with ITP. 64,65 Various other autoimmune disorders
1. Hermansky-Pudlak syndrome can coexist with pernicious anemia, including autoimmune vitiligo
66
2. Chédiak-Higashi syndrome and autoimmune thyroiditis. Abnormalities of platelet function are
67,68
3. Griscelli syndrome sometimes seen associated with vitamin B deficiency. Diminished
12
platelet aggregation and reduced release of ADP and ATP from granule
C. α- and dense granule defects stores in response to different agonists have been reported, and vita-
IV. Disorders of platelet surface receptors min deficiency has been suggested to induce an acquired storage pool
A. Glycoprotein (GP) Ib-IX-V defects disease (Chap. 41). 68
1. Bernard-Soulier syndrome Copper deficiency is usually seen in patients who have undergone
2. Platelet-type von Willebrand disease gastric bypass surgery, and may cause anemia, leukopenia, and throm-
bocytopenia associated with neurologic deficits resembling vitamin B
12
3. Velocardiofacial syndrome deficiency. Patients with copper deficiency also may be misdiagnosed as
B. Integrin α β defects: variant forms of Glanzmann having MDS, because increased ring sideroblasts and dysplastic precur-
IIb IIIa
thrombasthenia sor cells can be seen on marrow smears. 69,70
V. Wiskott-Aldrich syndrome (WAS) protein-related Acute and chronic alcohol (ethanol) consumption affects hemato-
disorders poiesis and blood cell survival both directly and indirectly. Alcohol is
A. Classical Wiskott-Aldrich syndrome one of the leading causes of thrombocytopenia in Western countries.
B. X-linked thrombocytopenia Acute ethanol intoxication in healthy volunteers induces thrombocy-
71
C. X-linked neutropenia topenia. Platelet counts in these cases are usually mildly decreased
9
VI. GATA-1 mutations (generally more than 100 × 10 /L); severe thrombocytopenia is quite
rare. Acute ethanol-induced thrombocytopenia usually resolves within
A. X-linked thrombocytopenia 5 to 21 days with cessation of ethanol ingestion, sometimes with a tran-
B. X-linked thrombocytopenia and thalassemia-like sient rebound thrombocytosis that may reach up to 1,000,000 × 10 /L.
9
72
phenotype Although the mechanism of acute alcohol-related thrombocytopenia is
C. Congenital erythropoietic porphyria not clear, it has been suggested that metabolites of ethanol, especially
VII. Ankyrine repeat domain (ANKRD)-26 mutations acetaldehyde, impair the late stages of platelet production and increase
73
A. Moderate thrombocytopenia with mild bleeding ten- platelet destruction. Thus, thrombocytopenia associated with acute
dency, dysmegakaryopoiesis, increased risk of myeloid alcohol ingestion would be expected to be more frequent in those with
malignancies poor nutrition (delayed oxidation of acetaldehyde) and those with par-
VIII. RUNX-1 mutations tial acetaldehyde dehydrogenase defiance. Thrombocytopenia induced
A. Familial platelet disorder with propensity to myeloid by alcohol ingestion is accompanied by a decreased number of mar-
row megakaryocytes. Vacuolated proerythroblasts and granulocyte
malignancy (FDP/AML)
IX. Miscellaneous precursors are sometimes seen, as are multinuclear erythroblasts and
74
megaloblasts. Vacuolization of the periphery of mature megakaryo-
A. Sitosterolemia cytes has been reported. Alcoholism (chronic ethanol consumption,
75
B. Montreal platelet syndrome which is defined as consumption of more than 80 g of ethanol per day),
C. Others on the other hand, may cause thrombocytopenia by other mechanisms,
such as alcoholic liver cirrhosis (both splenomegaly and thrombopoi-
etin deficiency), folic acid deficiency, and alcohol-induced marrow
suppression. 74–78

Kaushansky_chapter 117_p1993-2024.indd 1998 9/21/15 2:31 PM