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1988 Part XII: Hemostasis and Thrombosis Chapter 116: Classification, Clinical Manifestations, and Evaluation of Disorders of Hemostasis 1989

13. Habitual spontaneous abortions raise the possibility that the However, performing an initial set of widely available and inexpensive
patient has a quantitative or qualitative abnormality of fibrinogen tests, including prothrombin time (PT), activated partial thromboplas-
(Chap. 125), factor XIII deficiency (Chap. 124), or the antiphospho- tin time (aPTT), and platelet count, is important for the following rea-
lipid syndrome (Chap. 131). There is also an association between sons: (1) The patient’s history sometimes is unreliable; (2) the patient
infertility and spontaneous abortion in patients with inherited may have a mild hemostatic abnormality that has not manifested itself
thrombophilia (Chap. 130). for lack of hemostatic challenge; (3) the patient may have developed
14. Hemarthroses are the hallmark abnormality in the hemophiliac; an acquired hemostatic defect that has remained asymptomatic; and
they are rare in other disorders except in severe factor VII defi- (4) the tests may reveal more than one abnormality. 9
ciency and type 3 von Willebrand disease (Chaps. 124 and 126). Figure 116–1 shows a series of algorithms that integrate the
Because discoloration of the skin overlying the joint with hemar- patient’s bleeding history and the results of the initial hemostatic tests.
throses does not occur, patients may not recognize that their A prolonged aPTT as a sole abnormality can be caused by a deficiency
symptoms (pain, swelling, and limitation of motion) are caused by of factor VIII, IX, XI, or XII; presence of heparin; or by an inhibitor,
bleeding into their joints. which can be either factor specific, such as an antibody against factor
15. Excessive hemorrhage associated with surgical procedures is com- VIII, or factor nonspecific, such as the presence of heparin or a lupus
mon in patients with hemorrhagic disorders. Procedures involving anticoagulant (Fig. 116–1A). A prolonged PT as the sole finding can
tissues with increased local fibrinolytic activity like urinary tract, indicate a factor VII deficiency, a mild vitamin K deficiency, or the pres-
nose, tonsils and oral cavity are particularly prone to bleed. ence of an inhibitor (Fig. 116–1B). Abnormalities of both PT and aPTT
16. Excessive bleeding following circumcision is common in males with may indicate a deficiency of fibrinogen, prothrombin, factor V or factor
severe hemostatic disorders such as hemophilia A, hemophilia B, or X, an inhibitor to one of these factors, or a combined deficiency of coag-
Glanzmann thromboasthenia, and often is the patient’s first symptom. ulation factors (Fig. 116–1C).
17. Bleeding from the umbilical stump is characteristic of factor XIII To distinguish between a deficiency state and the presence of an
deficiency (Chap. 124) and afibrinogenemia (Chap. 125). inhibitor, repeating the abnormal test, the PT and/or aPTT, using a 1:1
mixture of the patient’s plasma and normal plasma is useful. If the mix-
ture normalizes the prolonged PT or aPTT, a deficiency state is likely, as
PHYSICAL EXAMINATION most coagulation tests are calibrated to produce a normal result if each
of the relevant factor levels are 50 percent of normal or greater. If the
Physical examination is essential for identifying signs of bleeding or mixture still yields a significantly prolonged PT or aPTT, an inhibitor
their sequelae and for signs of a possible underlying disorder that can probably is present. Some inhibitors, such as antibodies to factor VIII,
cause the hemostatic derangement (see Table 116–1). Careful exami- require time to inhibit the factor VIII activity in the assay, whereas
nation of the skin is essential for detecting petechiae and ecchymoses. other inhibitors, such as lupus anticoagulant or heparin, do not. Conse-
These signs may be prominent on the legs, where the hydrostatic pres- quently, incubating the mixture for 1 or 2 hours at 37°C before perform-
sure is greatest, or around the hair follicles in vitamin C deficiency. ing the coagulation assay is desirable.
Telangiectasias may range from pinpoint erythematous dots that When none of the initial test results (PT, aPTT, and platelet count)
blanch with pressure to classic cherry angiomata ranging in size up to is abnormal and the patient exhibits bleeding manifestations, ristocetin
several centimeters. Many normal individuals develop increasing num- cofactor (RCF) or von Willebrand factor activity and examination of
bers of telangiectasias with aging. Patients with hereditary hemorrhagic the blood film can be helpful for distinguishing among various candi-
telangiectasia have more florid lesions that characteristically affect the date hemostatic abnormalities. The bleeding time is not used anymore
vermilion border of the lips and the tongue (including the underside because the test is highly operator and situational (room temperature,
of the tongue), but not all patients have these classic features. Thus, a skin circulation, etc.) dependent and is not sufficiently reliable to be
systematic search of the integument is necessary. Spider telangiectasias useful in the diagnostic process. Instead, many laboratories have intro-
found in patients with chronic liver disease have a more splotchy and duced the platelet function analyzer (PFA) to detect qualitative defects
serpiginous appearance than the telangiectasias associated with heredi- in primary hemostasis. Figure 116–2 shows an algorithm that includes
tary hemorrhagic telangiectasia. In addition, the telangiectasias tend to these secondary tests. Patients with type 1 and type 2 von Willebrand
be concentrated on the shoulders, chest, and face. disease often have normal findings on initial laboratory tests because
Chapter 122 details the differential diagnosis of nonpalpable pur- factor VIII levels are sufficiently high (>30 U/dL) for a normal aPTT
puras and palpable purpuras. Hematomas, ecchymoses, and protracted result (Chap. 126). Examination of the blood film is helpful for distin-
oozing should be sought at venipuncture sites, injection sites, and arte- guishing between Bernard-Soulier syndrome and von Willebrand dis-
rial and venous catheter insertion sites. Joint deformities and limited ease because giant platelets are characteristic of the former (Chap. 120).
joint mobility are suggestive of severe hemophilia A or B, severe defi- Distinguishing mild-type von Willebrand disease from normal is diffi-
ciency of factor VII, or type 3 von Willebrand disease (Chaps. 123, 124, cult because levels of von Willebrand factor in the normal population is
and 126). Hyperelasticity of the skin and hyperextensibility of joints are highly variable, partly accounted for by differing von Willebrand factor
typical of Ehlers-Danlos syndrome, and hyperextensibility of only the levels in individuals with different ABO blood types. In fact, some inves-
thumb probably is a variant. 8
tigators have questioned whether patients with von Willebrand factor
levels as low as 35 percent should be labeled as having von Willebrand
EVALUATION BASED ON BLEEDING disease. The likelihood of having von Willebrand disease is a function
10
HISTORY, PHYSICAL EXAMINATION, of bleeding history, the von Willebrand factor level, and the number
of first-degree family members with reduced von Willebrand factor
AND BASIC LABORATORY TESTS levels. 11
The ristocetin-induced platelet aggregation test is useful for dis-
The patient’s history and results of physical examination provide tinguishing type 2B and platelet-type von Willebrand disease from the
important information on the likelihood of the patient having a hemo- other types of von Willebrand disease. In type 2B and platelet-type
static defect and the possible cause of the defect, if one is present. von Willebrand disease, an enhanced response to low concentrations

Kaushansky_chapter 116_p1985-1992.indd 1988 9/18/15 10:13 AM