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HEMOPHILIA
increased bleeding by 1 yr. of age.
The hallmark of hemophilic bleeding is hemarthrosis. Bleeding into the
joints may be induced by minor trauma; many hemarthroses are
Hemophilia A (factor VIII deficiency) and hemophilia B (factor IX spontaneous. Earliest joint hemorrhages appear most commonly in
deficiency) are the most common and serious congenital the ankle.
coagulation factor deficiencies. Clinical findings are virtually identical. They complain of a warm, tingling sensation in the joint as the first sign
Hemophilia C: Factor XI. AD. Frequent in Ashkenazi Jews, of an early joint hemorrhage. Bleeding into the iliopsoas muscle
Replacement therapy should be considered and given requires specific mention. A patient may lose large volumes of blood
preoperatively, depending on the nature of the surgical procedure. into the iliopsoas muscle, verging on hypovolemic shock, with only a
Fresh-frozen plasma (FFP) is used. Patients undergoing dental vague area of referred pain in the groin. The hip is held in a flexed,
extractions can be monitored closely and may benefit from treatment internally rotated position owing to irritation of the iliopsoas. The
with fibrinolytic inhibitors like aminocaproic acid, with plasma diagnosis is made clinically from the inability to extend the hip but
replacement therapy used only if hemorrhage occurs. PTT is often must be confirmed with ultrasonography or CT.
longer than it is in patients with either severe factor VIII or factor IX Treat first, image second!
deficiency. This may also be confirmed by specific assays. Half-life of Life-threatening hemorrhages require replacement therapy to
factor XI: 48 hr, maintaining adequate levels of factor XI commonly is achieve a level equal to that of normal plasma (100 IU/dL, or 100%).
not difficult. Patients with mild hemophilia who have factor VIII or factor IX levels >5
Factors VIII and IX participate in a complex required for the activation IU/dL usually do not have spontaneous hemorrhages. These
of factor X. Together with phospholipid and calcium, they form the individuals may experience prolonged bleeding after dental work,
tenase, or factor X activating, complex. In vivo, the complex of surgery, or injuries from moderate trauma and may not be diagnosed
factor VIIa and tissue factor activates factor IX to initiate clotting. until they are older.
In the laboratory, prothrombin time (PT) measures the activation of The laboratory screening test that is affected is PTT. In severe
factor X by factor VII and is therefore normal in patients with factor VIII hemophilia, the PTT value is usually 2-3 times the upper limit of normal.
or factor IX deficiency. Results of the other screening tests of the hemostatic mechanism
After injury, the initial hemostatic event is formation of the platelet (platelet count, bleeding time, prothrombin time, and thrombin time)
plug, together with the generation of the fibrin clot that prevents are normal.
further hemorrhage. Specific assay for factors VIII and IX will confirm the diagnosis of
In hemophilia A or B, clot formation is delayed and is not robust. hemophilia. If correction does not occur on mixing, an inhibitor may
Inadequate thrombin generation leads to failure to form a tightly be present.
cross linked fibrin clot to support the platelet plug. Patients with Severe hemophilia is characterized as having <1% activity of the
hemophilia slowly form a soft, friable clot. When untreated bleeding specific clotting factor, and bleeding is often spontaneous.
occurs in a closed space, such as a joint, cessation of bleeding may Moderate hemophilia has factor levels of 1-5% and usually require
be the result of tamponade. mild trauma to induce bleeding.
With open wounds, in which tamponade cannot occur, profuse Mild hemophilia has levels >5%, may go many years before the
bleeding may result in significant blood loss. condition is diagnosed, and frequently require significant trauma to
The clot that is formed may be friable, and rebleeding occurs during cause bleeding.
the physiologic lysis of clots or with minimal new trauma. The genes for factors VIII and IX are carried near the terminus of the
Neither factor VIII nor factor IX crosses the placenta; bleeding long arm of the X chromosome and are therefore X linked traits.
symptoms may be present from birth or may occur in the fetus. African-Americans often have a different factor VIII haplotype, and
Only 2% of neonates with hemophilia sustain intracranial this difference may be the reason that African-Americans have higher
hemorrhages, and 30% of male infants with hemophilia bleed with inhibitor formation.
circumcision. Prophylaxis is the standard of care for most children with severe
Obvious symptoms such as easy bruising, intramuscular hematomas, hemophilia to prevent spontaneous bleeding and early joint
and hemarthroses begin when the child begins to cruise. Even in deformities.
PRIMARY BILIARY CIRRHOSIS Possibly asymptomatic, fatigue, pruritus, RUQ pain, fever, night sweats,
jaundice, xanthomas.
Is an idiopathic autoimmune disorder that occurs more often in Labs include increased alkaline phosphatase, increased FFT, normal
middle aged women. AST and ALT, increased cholesterol, increased bilirubin (total and
Autoimmune disease with intrahepatic bile duct destruction leading direct), possible positive perinuclear antineurophil, increased bilirubin
to accumulation of cholesterol, bile acids and bilirubin. (total and direct), possible positive perinuclear antineurtophil
Bilirubin levels do not elevate until the disease is extremely far cytoplasmic antibodies (pANCA); biopsy appears similar to that for
advanced, which is usually after 5-10 years. PBC.
It has as strong association with other autoimmune diseases such as The presentation and general laboratory tests are generally the same
Sjogren syndrome, RA and scleroderma. as those for primary biliary cirrhosis, except that the antimitochondrial
The most common symptoms are fatigue and pruritus. antibody test will be negative.
Some asymptomatic patients have elevated alkaline phosphatase The most specific test for primary sclerosis cholangitis is and ERCP or
level when measured for other reasons. Osteoporosis and transhepatic cholangiogram.
hypothyroidism are found in 20-30% of patients. This is the only chronic liver disease in which a liver biopsy is not the
Transaminases are often normal. The most common abnormality most accurate test.
Jaundice, xanthomas, skin hyperpigmentation, hepatosplenomegaly ERCP shows structuring and irregularity of extrahepatic and
is elevation of alkaline phosphatase and gamma glutamyl intrahepatic bile ducts. Example beads on string.
transpeptidase (GGTP). Total IgM levels are also elevated. Treatment includes endoscopic stenting of strictures; surgical
The most specific blood test is the antimitochondrial antibody. resection of affected ducts and liver transplant may be required in
Biopsy is always the best way to diagnose liver disease. It is the only progressive cases.
test more specific than antimitochondrial antibodies. Treatment is the same as for primary biliary cirrhosis with
Other labs: increased alkaline phosphatase, increased GGt, normal URSODEOXYCHOLIC ACID.
AST and ALT, increased cholesterol, increased bilirubin (total and Also liver transplant may be considered.
direct) later in disease course; positive antinuclear antibody (ANA).