Clin Med/Pathophys

Question 1

hemophilia

Answer 1

A/B are congenital, X linked recessive deficiencies in coagulation factors VIII / IV. severe cases present in infant males w spontaneous bleeding, mild cases present with significant hemostatic events (surgery or trauma)

Question 2

Deep Vein Thrombosis (DVT)

Answer 2

results from blood clot formation within large veins in the legs/pelvis.

Question 3

thrombocytopenia

Answer 3

relative decrease in platelets in the blood with a platelet count <100,000 (normal is 150,000-300,000). characteristically produce petechial and purpuric lesions and bleeding from mucous surfaces

Question 4

pulmonary embolism

Answer 4

blockage of the main artery of hoteling or one of its branches by a clot formation that has formed elsewhere and traveled through the bloodstream. most commonly results from DVT.

Question 5

vit K deficiency etiology

Answer 5

deficient dietary intake, malabsorption, decreased production by intestinal bacteria, primary liver dz depletes stores

Question 6

vit K deficiency pathophys

Answer 6

normally it k reductase assists in conversion of gamma-carboxyglutamic acid necessary for factors II, VII, IX, X. if deficient in bit k, clotting factor levels low, and will have prolonged PT

Question 7

vit K deficiency s/sxs

Answer 7

bleeding

Question 8

vit K deficiency mgmt

Answer 8

vit K PO or IV

Question 9

vit K deficiency prognosis

Answer 9

improvement in PT in 1 day w PO; 8-10hrs w IV

Question 10

disseminated intravascular coagulation (DIC) etiology

Answer 10

depletion of coagulation factor d/t bacterial sepsis, leukemia, lymphoma, or massive hemorrhage, burns, trauma, pregnancy, snake bites. concurrent uncontrolled generation of thrombin

Question 11

disseminated intravascular coagulation (DIC) pathophys

Answer 11

widespread intravascular fibrin formation: systemic fibrin deposition in small and medium vessels. massive bleeding d/t platelet and clotting factor depletion. (the clots are blocking small vessels, and all the clotting factors are being used up in those vessels, and not where they are actually needed.)

Question 12

disseminated intravascular coagulation (DIC) s/sxs

Answer 12

depends on magnitude of hemostasis imbalance: ranges from venipuncture oozing/ecchymosis/petechiae to uncontrolled bleeding throughout entire circulatory system. The clots can occlude blood flow to areas of body, as well.

Question 13

disseminated intravascular coagulation (DIC) dx workup

Answer 13

increased PT & aPTT. 
thrombocytopenia.
decreased fibrinogen levels.
increase in fibrin degradation products.
schistocytes on smear (fragmented RBCs)

Question 14

disseminated intravascular coagulation (DIC) mgmt

Answer 14

treat underlying cause. in high risk pts, can transfuse platelets, cryoprecipitate (for fibrinogen), fresh frozen plasma and packed RBCs. Heparin for clots.

Question 15

coagulopathy of liver disease etiology

Answer 15

cirrhosis or other hepatopathologies leading to impaired hepatic function. decreased synthesis of clotting factors II, VII, V, IX, and fibrinogen.

Question 16

coagulopathy of liver disease pathophys

Answer 16

fewer clotting factors available = net decrease in clotting ability

Question 17

coagulopathy of liver disease s/sxs

Answer 17

bleeding induced by any stressors. typically asymptomatic with incidentally finding on coagulation lab studies.

Question 18

coagulopathy of liver disease mgmt

Answer 18

FFP infusion if active bleeding present. cryoprecipitate if bleeding + fibrinogen level low. liver transplant. recombinant human activated factor VII.

Question 19

aplastic anemia etiology

Answer 19

bone marrow failure from suppression or injury to hematopoietic stem cells. inability to produce mature RBCs

Question 20

aplastic anemia pathophys

Answer 20

most common cause is autoimmune suppression of hematopoiesis by a T cell mediated cellular mechanism “idiopathic” aplastic anemia. SLE can cause stem cell dysfunction through IgG autoantibody.

Question 21

aplastic anemia s/sxs

Answer 21

anemia, fatigue/weakness, neutropenia leads to frequent infections, thrombocytopenia causes mucosal and skin bleeding

Question 22

aplastic anemia dx workup

Answer 22

pancytopenia, anemia also associated with reticulocytopenia.

Question 23

aplastic anemia mgmt

Answer 23

supportive care (erythropoietic and/or myeloid growth factors); severe cases may require BMT in meds, immunosuppression in adults.

Question 24

aplastic anemia complications

Answer 24

infection, bleeding disorders, anemia, death

Question 25

aplastic anemia prognosis

Answer 25

severe cases are rapidly fatal if left untreated

Question 26

immune thrombocytopenic purpura (ITP) etiology

Answer 26

hemorrhagic syndrome with diverse causes that can occur in an acute or chronic form. characterized by reduction in # of circulating platelets, abundant megakaryoctytes in the bone marrow, and a shortened platelet life span. may be idiopathic or secondary to a lymphoproliferative disorder, drugs or toxins, bacterial or viral infection, SLE, or other conditions.

Question 27

immune thrombocytopenic purpura (ITP)pathophys

Answer 27

circulating antiplatelet IgG autoantibody usually directed against a membrane protein, which is the fibrinogen receptor (glycoprotein IIb/IIIa). the spleen is primarily the site of platelet destruction and may also be a significant source of autoantibody production.

Question 28

immune thrombocytopenic purpura (ITP) s/sxs

Answer 28

acute onset: ecchymosis or showers of petechiae, may have bleeding gums, vaginal bleeding, GI bleeding, hematuria. chronic: insidious onset, often w long hx of bruising easily and menorrhagia. showers of petechiae may occur

Question 29

immune thrombocytopenic purpura (ITP) dx workup

Answer 29

labs: platelet count is mod to severely decreased. WBC & RBC usually normal although iron deficiency anemia may be present as a result of bleeding. bone marrow shows increased # of large megakaryocytes without platelet budding. bleeding time is prolonged. capillary fragility greatly increased. poor clot retraction. PTT/PT, and coat time are normal.

Question 30

immune thrombocytopenic purpura (ITP) mgmt

Answer 30

depends on age of pt, severity of dz, duration of thrombocytopneia, and clinical variant. secondary immune thrombocytopenia are best managed by tx the underlying primary disorder. pts with mild or no sxs don't nd tx but should avoid contact sports, elective surgeries, and unessential meds. corticosteroids can be used in pts with mod to severe purpura of short duration

Question 31

thrombotic thrombocytopenic purport (TTP) etiology

Answer 31

ADAMTS13 is reduced in amount or function, allowing persistence of many unusually LARGE vWF multimers; identification of these multimers is diagnostic for TTP.

Question 32

thrombotic thrombocytopenic purport (TTP) pathophys

Answer 32

association with ADAMTS-13 (von Willebrand factor [vWF]-cleaving protease) deficiency. oversized vWF results in platelet over activation leading to thrombus formation. microthrombi of agglutinated platelets form in microvasculature, occluding arterioles and capillaries. tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and interferon-gamma act in synergy to induce apoptosis in microvascular endothelial cells, but spare large vessels and pulmonary vessels

Question 33

thrombotic thrombocytopenic purport (TTP) s/sxs

Answer 33

classic pentad of TTP = microangiopathic hemolytic anemia, thrombocytopenia, neurological symptoms, renal failure, fever. Usually systemic, but can be localized. most common symptoms include: weakness, anorexia, vomiting, diarrhea, nausea. neurological symptoms: generalized headache, seizures, confusion, coma, transient ischemic attack (TIAs)

Question 34

thrombotic thrombocytopenic purport (TTP) dx workup

Answer 34

The hemolytic anemia is characterized by many circulating fragmented erythrocytes in the form of schistocytes and helmet cells. High lactate dehydrogenase (LDH) levels correlate with the severity of the disease. Renal manifestations include microscopic hematuria, rarely gross hematuria, mild to moderate proteinuria, and azotemia with up to 10% of patients having acute renal failure. Renal biopsy may show thrombi with a higher number of platelets and fewer erythrocytes or fibrin.

Question 35

thrombotic thrombocytopenic purport (TTP) mgmt

Answer 35

``` Corticosteroids + plasma exchange Low-dose aspirin when platelets recover Folate supplements Refractory cases consider: Ritixumab, Cyclophosphamide, Cyclosporine Splenectomy (severe cases) Red Cell Transfusion ```

Question 36

Hemolytic uremic syndrome (HUS) etiology

Answer 36

acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia. It is seen mostly in children and most cases are preceded by hemorrhagic diarrhea (E. Coli is the most common cause). Can present without preceding diarrhea (called DHUS) which is caused by dysregulation of the complement system.

Question 37

Hemolytic uremic syndrome (HUS) pathophys

Answer 37

Infection induced by GI illness with diarrhea (EHEC most common cause), has also been associated with invasive pneumococcal disease, or less commonly due to genetic abnormalities affecting the complement pathway. Damage may occur to the endothelial cells, mesangial cells, renal tubular epithelial cells, or monocytes. Proinflammatory and prothrombotic changes in the coagulation pathway may damage the endothelial cells and lead to organ damage.

Question 38

Hemolytic uremic syndrome (HUS) s/sxs

Answer 38

Prodromal GI illness with diarrhea, often bloody; symptoms of anemia; neuro symptoms (irritability, lethargy, confusion, stroke, seizures); possible jaundice from hemolysis

Question 39

Hemolytic uremic syndrome (HUS) dx workup

Answer 39

Hemolytic anemia – hct <30% with evidence of erythrocyte destruction on peripheral blood smear. Low platelet count. High serum creatinine.

Question 40

Hemolytic uremic syndrome (HUS) mgmt

Answer 40

Control of fluid/electrolyte imbalance; RBC transfusion for cardiovascular or respiratory compromise; control of hypertension; dialysis if acute renal failure unresponsive to fluid mgmt; nutritional support; avoid antimotility agents

Question 41

Hemolytic uremic syndrome (HUS) complications

Answer 41

Acute renal failure, chronic kidney dz, possible neurologic complications (seizures), acute heart failure, GI perforation or intestinal strictures.

Question 42

Henoch-Schonlein purpura etiology

Answer 42

Common systemic vasculitis. More commonly in children. Nonthrombocytopenic purpura caused by inflammation in the blood vessels of the superficial dermis. The dz usually occurs about 10 days after the start of a URI, but no single microorganism or environmental factor has been confirmed as the cause.

Question 43

Henoch-Schonlein purpura pathophys

Answer 43

Leukocytoclastic vasculitis and deposition of IgA in the walls of involved blood vessels (typically small vessels). This is a form of vasculitis characterized by IgA dominant immune deposits in the vessel walls, small-vessel involvement (capillaries, venules, arterioles), with skin/gut/renal/and joint manifestations.

Question 44

Henoch-Schonlein purpura s/sxs

Answer 44

Acute onset fever, palpable purpura on lower extremities (but can also be seen on hands/arms/trunk/buttocks), abdominal pain (typically colicky and worse after eating, the result of edema of the bowel wall & hemorrhage induced by mesenteric vasculitis), arthritis (most commonly the knees and ankles), hematuria (signals the presence of a glomerular lesion that is usually reversible, although it occasionally may progress to chronic kidney dz).

Question 45

Henoch-Schonlein purpura dx workup

Answer 45

Skin biopsy can demonstrate leukocytoclastic vasculitis with IgA deposition. Kidney biopsy shows segmental glomerulonephritis with crescents and mesangial deposition of IgA. Diagnosis should be confirmed by biopsy.

Question 46

Henoch-Schonlein purpura mgmt

Answer 46

NSAIDS may alleviate arthralgias, but can aggravate GI symptoms and should be avoided in pts with renal dz. Dapsone (100mg/day) may be effective, maybe through interference with the interactions of IgA and neutrophils, but not really known. Glucocorticoids may help with the joint/GI symptoms, but not with the rash or the renal dz.

Question 47

Henoch-Schonlein purpura prognosis

Answer 47

The dz is self-limited most of the time, resolving within a few weeks.

Question 48

Heparin induced thrombocytopenia etiology

Answer 48

Thrombocytopenia within 5-10 days of exposure to heparin. Decline in baseline platelet count of 50% or greater. Affects about 3% of pts who are exposed to unfractionated heparin and .6% of pts who are exposed to low-molecular wt heparin

Question 49

Heparin induced thrombocytopenia pathophys

Answer 49

Results from the formation of IgG antibodies to heparin-platelet factor 4 complexes. The antibodies then bind platelets, which activates them. This platelet activation leads to both thrombocytopenia and a pro-thrombotic state.

Question 50

Heparin induced thrombocytopenia s/sxs

Answer 50

Usually asymptomatic. Bleeding does not usually occur.

Question 51

Heparin induced thrombocytopenia mgmt

Answer 51

Immediate discontinuation of the heparin. Platelet transfusions are rarely necessary. Direct Thrombin Inhibitor: Argatroban administered immediately and should be continued until the platelet count has recovered to at least 100,000/mcL, at which point treatment with a vitamin K agonist (Warfarin) should be initiated.

Question 52

Factor VIII deficiency (Hemophilia A) etiology

Answer 52

X-linked recessive genetic disorder of clotting factor VIII

Question 53

Factor VIII deficiency (Hemophilia A) pathophys

Answer 53

Genetic Factor VIII needs to be activated in the intrinsic pathway, so that factor X can be cleaved & eventually lead to a fibrin crosslinked clot. Bleeding results from altered clot formation

Question 54

Factor VIII deficiency (Hemophilia A) s/sxs

Answer 54

excessive bleeding w/ or w/o trauma: bleeding into joints, epistaxis. hemorrhage disproportionate to trauma. spontaneous hemorrhage (joints, muscles, CNS, GI, & GU all common locations). family h/o bleeding.

Question 55

Factor VIII deficiency (Hemophilia A) d/dx

Answer 55

- -CALF DIPS mnemonic: Cirrhosis/ liver dz, Asa& other NSAIDs, Leukemia, Factor VIII or IX dysfunction, Disseminated intravascular coagulation, Ideopathic thrombocytopenic purpura, Platelet deficiency, Scurvy - -if pt. reports weight loss also: cancer, HIV, RA, SLE, thyroid dz, renal dz - -vWD, deficiency of other clotting factors, other hemophilias

Question 56

Factor VIII deficiency (Hemophilia A) mgmt

Answer 56

factor VIII,Prompt, aggressive management of hemorrhages, Antihemolytic agents (desmopressin), monoclonal Abs (rituximab)

Question 57

Factor VIII deficiency (Hemophilia A) dx workup

Answer 57

CBC: normal to low Hg & platelet count; Factor VIII assay; coagulation study: normal to severely prolonged aPTT w/ a normal PT & bleeding time; Can do genetic testing

Question 58

Von Willibrand Dz (vWF) etiology

Answer 58

Autosomal dominant genetic mutation in VWF gene resulting in a quantitative or qualitative defect in vWF; most frequent bleeding disorder (1% prevalence), affects males & females; poor platelet adhesion to vascular walls and deficient factor VIII availability

Question 59

Von Willibrand Dz (vWF) pathophys

Answer 59

vWF is made & stored in endothelial cells & platelets. vWF allows platelets to resist the force of blood flow & adhere to exposed collagen of damaged vessel walls. vWF is also a carrier protein for clotting factor VIII. → vWF defect prevents proper platelet plug formation and stalls clotting cascade @ factor VIII

Question 60

Von Willibrand Dz (vWF) s/sxs

Answer 60

excessive bleeding (easy bruising, bleeding gums, epistaxis, menorrhagia). bleeding into joint is rare.

Question 61

Von Willibrand Dz (vWF) dx workup

Answer 61

Prolonged bleeding time, low vWF, low factor VIII procoagulant levels, decreased platelet aggregation when ristocetin is added to plasma

Question 62

Von Willibrand Dz (vWF) mgmt

Answer 62

varies depending on type/ subtype involved; Tx & prevent bleeding complications: desmopressin acetate, cryoprecipitate fresh, frozen plasma, factor VIII concentrate

Question 63

Factor IX deficiency (Hemophilia B) etiology

Answer 63

X-linked recessive genetic disorder (point mutations & deletions of F9 gene on long arm of X chromosome; generally inherited, but spontaneous mutation & mut. after infection have been seen)

Question 64

Factor IX deficiency (Hemophilia B) pathophys

Answer 64

Deficiency of functional factor IX= insufficient thrombin produced by intrinsic pathway, so only platelet plug forms. Lack of crosslinked fibrin clot enables easy bleeding

Question 65

Factor IX deficiency (Hemophilia B) s/sxs

Answer 65

excessive bleeding w/ or w/o trauma: bleeding into joints, epistaxis. hemorrhage disproportionate to trauma. spontaneous hemorrhage (joints, muscles, CNS, GI, & GU all common locations). family h/o bleeding.

Question 66

Factor IX deficiency (Hemophilia B) dx workup

Answer 66

CBC: normal to low Hg & platelet count; Factor IX assay; coagulation study: normal to severely prolonged aPTT w/ a normal PT & bleeding time; Can do genetic testing

Question 67

Factor IX deficiency (Hemophilia B) mgmt

Answer 67

factor IX,Prompt, aggressive management of hemorrhages, Antihemolytic agents (desmopressin), monoclonal Abs (rituximab)