Page 2165 - Hematology_ Basic Principles and Practice ( PDFDrive )

1918 Part XII Hemostasis and Thrombosis

The Laboratory Manifestations of Bleeding Disorders TABLE Differential Diagnosis of Bleeding Problems
128.1
The laboratory manifestations of bleeding disorders can include abnor-
malities from the following: Major Categories Comments
1. The underlying hemostatic defect No bleeding Symptoms do not reflect a bleeding disorder and
2. Bleeding complications (e.g., anemia, iron deficiency, disorder have another explanation (e.g., a surgical
coagulopathy secondary to hemodilution after resuscitation bleed, not caused by a bleeding disorder).
for a massive bleed, development of red cell antibodies after
transfusion) Possible The laboratory findings are nondiagnostic, and
3. False-positive abnormalities (e.g., prolonged aPTT caused by bleeding the bleeding history is considered equivocal
incidental mild factor XII deficiency, which is found in about 1 of disorder (e.g., unexplained serious bleed with one
200 patients, or a lupus anticoagulant, which can be a transient surgical procedure; unexplained menorrhagia
finding in about 5% of hospitalized patients) without other bleeding problems).
4. Extremes of normal variation (e.g., mildly low von Willebrand
factor levels in an individual who is blood group O, absent Definite The bleeding history is consistent with a bleeding
secondary aggregation with epinephrine in adjusted platelet bleeding disorder; however, the laboratory findings are
rich–plasma aggregation studies). disorder, nondiagnostic. Commonly the bleeding history
undefined or resembles mild to moderate defects in platelet
indeterminate function or von Willebrand factor. The
type diagnosis should only be made once an
adequate evaluation for common bleeding
to patients with acquired bleeding problems that suggest this pos- disorders (e.g., for von Willebrand disease and
sibility (e.g., bleeding associated with obesity, the development of platelet aggregation and release defects) is
type 2 diabetes, hypertension, striae, and/or changes in physical completed. If testing is not complete, the
appearance). classification should indicate the types of
The investigations for a bleeding problem typically also include conditions excluded or not excluded, for
screening tests (prothrombin time, aPTT, thrombin clotting time, example: mild mucocutaneous bleeding
and fibrinogen level), which are inexpensive tests, that detect problem, von Willebrand disease excluded,
acquired coagulopathies much more commonly than they detect mild mucocutaneous bleeding problem,
inherited bleeding disorders because of differences in prevalence. platelet release defects not yet excluded.
These investigations are useful as a baseline for individuals at risk Definite The symptoms and laboratory findings are
for developing a dilutional coagulopathy from bleeding and as initial bleeding considered diagnostic of a bleeding disorder.
investigations of a possible inherited or acquired coagulation disorder. disorder with Tables 128.2 and 128.3 summarize many of
Abnormalities, if detected, require further evaluation to determine a defined the potential inherited and acquired causes.
if the cause is a fibrinogen disorder or a deficiency of one or more cause
coagulation factors. Screening tests for von Willebrand disease
are warranted for individuals with a personal or familial history
9
of mucocutaneous bleeding. Platelet function disorders should be
evaluated by aggregation tests and tests for dense granule release, if
available, because these tests are useful for assessing common bleeding PROGNOSIS
disorders. 15,19,30 Chapter 129 provides more detail on the specific diag-
nostic tests that are appropriate for a laboratory workup of bleeding The prognosis for bleeding problems depends on the severity and
problems. nature of the hemostatic defect, exacerbating factors, and whether
these problems can be readily corrected (e.g., vitamin K to correct a
deficiency, discontinuing aspirin) or if they require hemostatic thera-
DIFFERENTIAL DIAGNOSIS OF BRUISING AND BLEEDING pies, such as factor concentrates and/or drugs (e.g., desmopressin,
tranexamic acid, or aminocaproic acid). Life expectancy is generally
The initial differential diagnosis should focus on three major catego- normal unless there is a severe bleeding disorder (e.g., severe hemo-
ries (Table 128.1): deciding whether there is (1) no bleeding disorder, philia) or a complication (e.g., transfusion-acquired chronic hepatitis
(2) a possible bleeding disorder (equivocal bleeding history and or human immunodeficiency virus). The prognosis for some rare
nondiagnostic laboratory findings), or (3) a definite bleeding disorders significantly improves after puberty (e.g., factor IX Leyden).
disorder. A few show progressive worsening over time (e.g., development of
There are many potential inherited and acquired causes of definite aplasia from congenital amegakaryocytic thrombocytopenia, transfor-
bleeding problems (summarized in Tables 128.2 and 128.3). The mation of thrombocytopenia from an inherited RUNX1 mutation
history should be evaluated to determine if the problems suggest a into myelodysplasia or acute myeloid leukemia). Other disorders
defect in the initial control of bleeding (e.g., defects in platelet adhe- (e.g., acquired hemophilia) may go into complete remission after
sion from von Willebrand disease or a platelet problem) or if there immunosuppressive treatment with risk for later relapses.
are delayed bleeding problems that suggest a defect in a coagulation Mild platelet function disorders, mild type 1 von Willebrand
factor or a fibrinolytic protein. Laboratory findings are important for disease, and many common undefined conditions that cause mucocu-
distinguishing undefined bleeding problems from von Willebrand taneous bleeding usually respond well to prophylactic desmopressin
disease and platelet function disorders, because their symptoms are therapy, which is given to prevent bleeding with major surgical
quite similar. 1,3,18,30 and dental procedures or bleeding with childbirth. Nonetheless,
Acquired bleeding problems arising from drugs are often diag- it is important to have a specific diagnosis to manage situations
nosed solely on the basis of the medical history (i.e., acquired bleeding in which desmopressin therapy alone is insufficient to control
problems that occurred while taking a medication that inhibits bleeding.
coagulation or platelet function), although laboratory testing can be Women with bleeding disorders have a similar prognosis to men,
useful to rule out other causes. The subject’s medical history and although they often have a greater burden of symptoms because of
1,3
laboratory findings are helpful for determining if there is a possibility menorrhagia and childbirth-related bleeding. Their outcomes with
of acquired bleeding problems from a bone marrow disorder, liver pregnancy and childbirth are often similar to individuals without
disease, renal failure, or an endocrine disorder (e.g., hypothyroidism bleeding disorders provided that they receive treatment to control
1,3
or, less commonly, Cushing syndrome). bleeding with delivery. However, some disorders have sufficiently