Hemorrhagic Disorders and Laboratory Assessment (Part 1)

Bleeding symptoms
▪ Most bleeding occurs as the result of an injury, bleeding may take the form of easy or
spontaneous bruising, internal bleeds, or hemorrhage.
▪ Hemorrhage is excessive bleeding that requires medical or physical intervention
▪ Bleeding may be local or general, mucocutaneous or anatomic, acquired or congenital.

1. Localized versus Generalized Hemorrhage

Localized Hemorrhage
➢ Bleeding from a single location usually indicates injury, infection, tumor, or an isolated
blood vessel defect and is called localized bleeding or localized hemorrhage.
➢ Example: inadequately cauterized or ineffectively sutured surgical site or an
arteriovenous malformation (AVM)
➢ Except for AVMs, localized bleeding seldom implies a blood vessel defect.
➢ In contrast, a qualitative platelet defect, a reduced platelet count (thrombocytopenia),
or a coagulation factor deficiency cause systemic and not localized bleeding

Generalized Hemorrhage
▪ Bleeding from multiple sites, spontaneous and recurring bleeds, or a hemorrhage that
requires physical intervention
▪ potential evidence for a disorder of primary hemostasis such as a blood vessel or
platelet defect or thrombocytopenia; or secondary hemostasis characterized by single
or multiple coagulation factor deficiencies or uncontrolled fibrinolysis.
▪ can either be:
▪ Mucocutaneous – typically in skin or orifices
▪ Anatomic – soft tissue, muscles, joints, deep tissue

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2. Mucocutaneous versus Anatomic Hemorrhage
Mucocutaneous Hemorrhage
▪ May appear as:
▪ Petechiae (red pinpoint spots)
▪ Purpura (purple skin lesions greater than 3 mm diameter)
▪ Ecchymoses (bruises) greater than 1 cm, typically seen after trauma
▪ Other symptoms of a primary hemostasis defect include bleeding from the gums,
epistaxis (uncontrolled nosebleed), hematemesis (vomiting of blood), blood in the urine
or stool, and menorrhagia (profuse menstrual flow)
▪ most likely to be associated with thrombocytopenia, qualitative platelet disorders ,von
Willebrand disease (VWD), or vascular disorders such as scurvy or telangiectasia.
▪ A thorough patient history and physical examination may distinguish between
mucocutaneous and anatomic bleeding; this distinction helps direct investigative
laboratory testing and subsequent treatment.

Anatomic (soft tissue) hemorrhage

▪ seen in acquired or congenital defects in secondary hemostasis such as plasma
coagulation factor deficiencies (coagulopathies)
▪ Examples:
▪ recurrent or excessive bleeding after minor trauma, dental extraction, or a
surgical procedure
▪ hemorrhage may immediately follow a primary event, but it is often delayed or
recurs minutes or hours after the event.
▪ May even be spontaneous
▪ Most are internal, such as (bleeds into joints (hemarthroses), body cavities, muscles, or
the central nervous system)

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3. Acquired versus Congenital Bleeding Disorders
Acquired Bleeding Disorders
▪ If a patient’s bleeding episodes begin after childhood, are associated with some disease
or physical trauma, and are not duplicated in relatives
▪ Liver disease, kidney failure, chronic infections, obstetric complications, anemia, dietary
deficiencies such as vitamin C or vitamin K deficiency, blunt or penetrating trauma, and
inflammatory disorders may all be associated with bleeding

Congenital Bleeding Disorders

▪ Uncommon, occurring in fewer than 1 per 100 people

▪ Usually diagnosed in infancy or during the first years of life.
▪ There may be first degree relatives with similar symptoms.
▪ lead to recurrent hemorrhages (spontaneous/ after minor injury or in unexpected
locations: (joints, body cavities, retinal veins and arteries/ CNS)
▪ Patients with mild congenital hemorrhagic disorders may have no symptoms until they
reach adulthood or experience some physical challenge (trauma, dental extraction, or a
surgical procedure)
▪ The most common congenital deficiencies:
▪ VWD, factor VIII (FVIII, hemophilia A) and factor IX deficiencies (FIX, hemophilia
B), platelet function disorders.

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Acquired Coagulopathies

1. Trauma induced Coagulopathy

▪ Accounts for most instances of fatal hemorrhage, and 3000 to 4000 haemorrhage
related deaths can be prevented through coagulopathy management.
▪ Coagulopathy
any single or multiple coagulation factor or platelet deficiency, and
▪ TIC
triggered by the combination of injury-related acute inflammation, hypothermia,
acidosis, and hypoperfusion (poor distribution of blood to tissues associated with
low blood pressure), all of which are elements of systemic shock.

Involves:
1. Massive Transfusion- within 24 hours, loss of 50% of blood volume within a 3-hour period,
2. Plasma- Fresh frozen plasma
3. Platelet Concentrate
4. Concentrates- reduce TRALI and TACO and Monitoring Therapy

2. Liver disease coagulopathy

▪ May be localized or generalized, mucocutaneous or anatomic.
▪ Alters the production of the vitamin K-dependent factors II (prothrombin), VII, IX, and X
and control proteins C, S, and Z.
▪ Declining coagulation factor V activity is a more specific marker of liver disease
▪ Fibrinogen (APR) – elevated -early or mild liver disease.
▪ Moderate thrombocytopenia occurs in one-third of patients with liver disease.
▪ Platelet aggregation and secretion properties are often suppressed;

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3. Chronic Renal Failure and Hemorrhage
▪ Often associated with platelet dysfunction and mild to moderate mucocutaneous
bleeding.
▪ Platelet adhesion to blood vessels and platelet aggregation -suppressed,
(guanidinosuccinic acid or phenolic compounds coat the platelets)
▪ Decreased RBC mass (anemia)
▪ thrombocytopenia contribute to the bleeding.
▪ Dialysis, RBC transfusions, or erythropoietin therapy (epoetin alfa, Procrit, Janssen
Pharmaceutica) may correct these disorders.

4. Vitamin K Deficiency and Hemorrhage

▪ Vitamin K, required for normal function of the vitamin K-dependent prothrombin group
of coagulation is ubiquitous in foods, especially green leafy vegetables, and the daily
requirement is small, so pure dietary deficiency is rare.
▪ Prolonged PT + with or without prolonged PTT

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 Occurs:
▪ Parenteral (intravenous) nutrition for an extended period
▪ Biliary duct obstruction (atresia), fat malabsorption, and chronic diarrhea
▪ Broad-spectrum antibiotics -disrupt normal gut flora- slight reduction because
they destroy bacteria that produce vitamin K
▪ Newborns (sterile intestines)
▪ g-carboxylation cycle of coagulation factors is interrupted coumarin-type oral
anticoagulants such as warfarin (Coumadin)

5. Autoanti-Factor Inhibitor and Acquired Hemophilia

▪ Autoanti-factor VIII is the most common.
▪ Patients who develop an autoantibody to factor VIII, which is diagnostic of acquired
hemophilia, are often older than 60 and have no apparent underlying disease.
▪ occasionally associated with rheumatoid arthritis, inflammatory bowel disease, systemic
lupus erythematosus, or lymphoproliferative disease.
▪ Pregnancy appears to trigger acquired hemophilia 2 to 5 months after delivery.
▪ In the presence of a factor VIII inhibitor, the PTT is likely prolonged, PT and TT -normal.
▪ A factor assay should reveal factor VIII activity to be less than 40 units/dL and the
activity level is often undetectable.

6. Acquired von Willebrand Disease

▪ With symptoms similar to those of congenital VWD:
▪ described in hypothyroidism, benign monoclonal gammopathies, Wilms tumor,
intestinal angiodysplasia, congenital heart disease, pesticide exposure, uremia,
lupus erythematosus, and autoimmune, lymphoproliferative, and
myeloproliferative disorders
▪ PT is not affected, the PTT may be moderately prolonged if the VWF reduction is severe
enough to reduce factor VIII to less than 40 units/dL, because VWF serves as the factor
VIII carrier molecule.

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7. Disseminated Intravascular Coagulation
▪ A significant complication of liver disease that is caused by decreased liver production of
regulatory antithrombin, protein C, or protein S and by the release of activated
procoagulants from degenerating liver cells.
▪ The failing liver cannot clear activated coagulation factors.
▪ Acute, uncompensated DIC, PT, PTT, and TT -prolonged, the fibrinogen level is reduced
to less than 100 mg/dL, and D-dimers are significantly increased.
▪ Chronic, compensated DIC-the only elevated test result may be the D-dimer assay
value, a hallmark of unregulated coagulation and fibrinolysis