Page 2166 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 128 Clinical Approach to the Patient With Bleeding or Bruising 1919

TABLE Differential Diagnosis of Congenital Bleeding Disorders
128.2
Disorder Comments
Fibrinogen deficiency or Deficiencies can be mild-moderate hypofibrinogenemia or severe afibrinogenemia. Fibrinogen function is abnormal in
dysfunction dysfibrinogenemias, which can present with bleeding, thrombosis, or both. Fibrinogen levels can be reduced in some
dysfibrinogenemias.
X-linked coagulation factor Presentation is influenced by the degree of deficiency. Factor VIII deficiency is more common than factor IX deficiency.
deficiencies—hemophilia If factor VIII is low, von Willebrand disease needs to be excluded as the cause.
Rarer, coagulation factor Deficiencies can affect factors XI, V, II, VII, or X, and the presentation is dependent on the severity of the deficiency.
deficiencies Hereditary deficiencies of multiple coagulation factors are rare (e.g., of factors V and VIII, or multiple vitamin K–
dependent coagulation factors for congenital defects impairing γ-carboxylation) and can easily be excluded by
measuring multiple factors.
Fibrinolytic defects Causes include disorders caused by loss of function, such as α 2 -antiplasmin or PAI-1 deficiency, and by gain-of-function
defects, such as Quebec platelet disorder (overexpression of urokinase plasminogen activator in megakaryocytes).
von Willebrand disease Causes include quantitative (partial type 1 to severe type 3) and qualitative defects (loss of function in type 2M and
2A, gain of function in type 2B and platelet-type). Type 1 von Willebrand disease can be confused with low von
Willebrand factor levels (e.g., because of blood group O).
Platelet disorders These conditions can affect platelet number, function, or both. The most common type of platelet function disorder is a
platelet secretion defect, which may or may not also impair aggregation responses. Disorders of platelet function are
commonly subclassified by the nature of the defect, such as the following:
1. Defects of membrane receptors for adhesive proteins (e.g., Glanzmann thrombasthenia and Bernard-Soulier
syndrome) or agonists (e.g., P2Y 12 deficiency)
2. Defects of signaling or secretion (the largest subcategory)
3. Cytoskeletal defects (e.g., MYH9-related disorders)
4. Storage pool disorders (e.g., gray platelet syndrome, dense granule deficiency, αγ-storage pool deficiency, Quebec
platelet disorder)
5. Defects of procoagulant function (e.g., Scott syndrome)
Vascular disorders Congenital vascular malformation, including hereditary hemorrhagic telangiectasia, Ehlers-Danlos syndrome
PAI-1, Plasminogen activator inhibitor 1.

good outcomes with childbirth that treatment for uncomplicated (endometrial ablation, hysterectomy) may be preferred options,
childbirth is not required (e.g., for Quebec platelet disorder). 7,28 particularly when menopause is not imminent.
Childbirth plans for women with bleeding disorders requires consid- General management of bleeding often includes supportive care,
eration of the options for pain management and avoidance of proce- correction and prevention of anemia (e.g., iron replacement for iron
dures, such as spinal or epidural anesthesia, to limit bleeding risks deficiency), and immunization against viruses that may be acquired
unless the defect can be readily corrected. by blood transfusion (e.g., hepatitis A and B) (see box on Case 6:
Illustration of Changes in Bleeding Outcomes With Treatment). If
the patient is immobilized or is undergoing a procedure with signifi-
THERAPY cant risks for thrombosis, there should be plans for thromboprophy-
laxis if the defect can be corrected during this treatment (e.g., by
An individual’s bleeding history is an important consideration when- factor replacement therapy for hemophilia or von Willebrand disease,
ever formulating therapeutic plans to control and minimize bleeding fibrinolytic inhibitor therapy for Quebec platelet disorder) or for
risks. Some symptoms do not warrant therapy (e.g., bruising), alternative thromboprophylaxis if this is not possible (e.g., use of
whereas treatment is important for controlling menorrhagia and for venous compression devices without anticoagulant drugs if the treat-
preventing and limiting challenge-related bleeding (e.g., from major ment will provide only brief hemostatic correction [e.g., desmopres-
or minor surgery and dental procedures, and traumas). For severe sin, platelet transfusions]). Other measures to limit bleeding risks
disorders, prophylactic treatment is warranted to prevent spontane- from bleeding disorders, with surgery, include the avoidance of
ous bleeding and to limit challenge-related bleeding, which can be intramuscular injections, spinal and epidural anesthesia, and NSAIDs
severe. The focus of therapy for some acquired conditions (e.g., for pain management. In older individuals with bleeding disorders
acquired hemophilia) is immunosuppressive therapy to achieve a and symptomatic atherosclerotic disease (e.g., angina), aspirin therapy
remission while managing any acute bleeding that warrants therapy. may be appropriate, with increased vigilance for signs and symptoms
For individuals with mild bleeding disorders, who have undergone of significant bleeding.
multiple prior surgical procedures without bleeding, it may be
appropriate to have treatment available (e.g., desmopressin on
“standby”) that is to be administered if and when abnormal bleeding FUTURE DIRECTIONS
occurs, provided that the procedural-related risks of bleeding are
small and readily managed (e.g., biopsy under local anesthetic) while The development of a bleeding-assessment tool with sufficient utility
waiting for the medication to have an effect. to distinguish persons with bleeding disorders from those without
For women with bleeding disorders, there are general treatments significant bleeding problems could improve the clinical assessment
that can be considered for symptomatic management regardless of of bleeding disorders. There is a need for more information on the
the type of bleeding disorder. For example, options for menorrhagia genetic causes of common disorders (e.g., type 1 von Willebrand
management include oral contraceptives, antifibrinolytic drugs, and disease, common platelet function disorders such as secretion defects)
hormone-releasing intrauterine devices. When menorrhagia limits to further understand bleeding disorder pathogenesis and bleeding
lifestyle and further pregnancies are not desired, surgical options risks.