Hematology

Question 1

Hemophilia

Answer 1

Definition: hereditary bleeding disorders due to deficiencies in factors VIII or IX. These result in the formation of unstable clot that can be easily dislodged, leading to excessive bleeding.

Question 2

Hemophilia is a *** linked disorder

Answer 2

X-linked Disorders

Question 3

Hemophilia A =

Answer 3

Factor VIII Deficiency

Question 4

Hemophilia B

Answer 4

= Factor IX Deficiency

Question 5

Diagnosis of Hemophilia

Answer 5

PT = normal
aPTT= PRLONGED
CBC/Plt = normal
Platlet aggregation studies - normal
mixing studies (normal)
specific factor assays (only way to differentiate A from B)

Question 6

which diagnostic lab for hemophilia?

Answer 6

aPTT is prolonged

Question 7

Hemophilia A

Answer 7

Most common type of hemophilia
X-linked recessive disorder resulting in deficiency in Factor VIII

S/sx: bleeding after injury or slight trauma, bleeding into muscles (pain and swelling, decreased ROM, erythema, and increased warmth), hemarthrosis, spontaneous bleeding episodes, excessive bruising/hematoma, fatigue.
Diagnosis: Factor VIII assay
PT and thrombin clotting time (TT) are normal
PTT or aPTT generally elevated but may be normal in mild disease
Treatment: none for mild signs and symptoms; infusion with Factor VIII concentrate

Question 8

Hemophilia B

Answer 8

X-linked recessive disorder resulting in deficiency in Factor IX
Males mainly affected (females are asymptomatic carriers)
S/sx: same as hemophilia A
Diagnosis: Factor IX assay
PT and thrombin clot time are normal
aPTT generally elevated but may be normal in mild disease
Treatment: none for mild signs and symptoms; infusion of Factor IX if severe

Question 9

Factor I

Answer 9

Fibrinogen Deficiency
Fibrinogen levels may be absent, decreased, or normal but non-functional

Question 10

Factor II

Answer 10

Prothrombin Deficiency

Question 11

Factor V

Answer 11

Parahemophilia, not the same as Factor V Leiden Deficiency

Question 12

Factor VII and X

Answer 12

acquired form is more common; due to vitamin K deficiency, severe liver diseases, and anti-coagulants use such as Warfarin

Question 13

Factor XI

Answer 13

hemophilia C, very common amongst Ashkenazi Jews, mild to moderate bleeding disorder

Question 14

Factor XII

Answer 14

no bleeding abnormality

Question 15

Factor VIIII

Answer 15

delayed bleeding, normal primary hemostasis; umbilical cord bleeding and intracranial hemorrhages are common

Question 16

Von Willebrand’s Disease

Answer 16

hereditary, anormal synthesis of von Willebrand factor (vWF), which causes reduced platelet adhesion and lower serum levels of factor VIII

Question 17

Von Willebrand’s disease

Answer 17

3x more common than hemophilia A, males/females affected the same

Question 18

Von Willebrands disease

Answer 18

heavy menses, epistaxis, easy bruising, GI bleeding, many people never diagnosed

Question 19

Von Willebrand Diagnostic labs

Answer 19

aPTT slightly prolonged, platlet aggregation studies (all normal except ristocetin), specific factor assays - show decreased factor VIII, vWF antigen - low.

Question 20

Thrombocytopenia

Answer 20

decreased platelet production. aplastic anemia, vitamin B12/folate deficiency, viral infections, leukemia, drugs.

increased destruction: ITP(immune), TTP (non-immune), increased sequestration: any causes of splenomegaly, such chronic liver disease/cirrhosis

Question 21

quantitative disorders

Answer 21

thrombocytopenia, thrombocytosis

Question 22

qualitative disorders

Answer 22

adhesion defects (vWD0), aggregation defects (DIC), secretion defects

Question 23

essential thrombocythemia

Answer 23

thrombosis may be more common than bleeding

Question 24

inadequate platelet function

Answer 24

vWD, drugs (nSAIDs), systemic disorders (lupus, uremia), inhibiting prostaglandins (multiple myeloma)

Question 25

Idiopathic/Immune Thrombocytopenic Purpura (ITP)

Answer 25

Antibodies form against platelet membrane glycoproteins and destroying platelets due to Type II hypersensitivity, which inhibits clot-formation & hemostasis Commonly preceded by acute URI or other viral infection (antibody cross reactions), drugs and heavy metals (metabolites acting as haptens)

Question 26

ITP s/sx

Answer 26

S/sx: petechiae,, bleeding gums, nose bleeds, and intestinal bleeding, heavy menses, easy bruising, most serious complication being intracranial hemorrhage Diagnosis: low platelet count Normal RBC count, WBC count, coagulation studies History

Question 27

Acute ITP

Answer 27

Rapid onset bruising & petechiae Primarily in children, ages 2 – 6 years Second most common age group: young adults Usually cross-reaction between immune response to viral infection & platelet proteins 80% cases self-limited with resolution in 1-2 months 80% of patients, their platelet count return to normal within 12 months Lab: severe thrombocytopenia

Question 28

Chronic ITP

Answer 28

Primarily in females, ages 25 – 45 years Associated with autoimmune conditions, such as SLE, HIV, HCV, CLL Limited self-resolution Up to 10% of spontaneously resolution (usually within first 6 months) 1/3 to 2/3 will reach a stable disease with first line treatment (glucocorticoids or IV immune globulin/IVIG) Lab: degree of thrombocytopenia varies

Question 29

ITP diagnosis

Answer 29

CBC - thrombocytopenia

Question 30

Thrombotic Thrombocytopenic Purpura (TTP)

Answer 30

Rare, fatal disease. spontaneous and excessive thrombus formation. most patients develop DIC and lead to life threatening multisystem disorder

Question 31

TTP diagnosis (labs)

Answer 31

CBC, thrombocytopenia (plt count <20,000). low Hgb, low RBC, peripheral blood smear: fragmented RBC serum creatinine: mild elevation serum ldh: elevated

Question 32

Disseminated intravascular coagulation (DIC)

Answer 32

Acquired Characterized by intravascular coagulation with depletion of coagulation factors and platelets, which occludes blood supply to tissues and results in end-organ damage Always secondary to an underlying disease: Obstetrical complication (retained products of conception, abruptio placentae) Infection, especially bacterial with severe sepsis Malignancy, burns, transplant rejection

Question 33

DIC s/sx

Answer 33

S/sx: usually bleeding from at least 3 unrelated sites Bleeding: petechiae, ecchymoses, blood oozing, hematuria, epistaxis, gingival bleeding Thrombosis: cough and dyspnea, leg pain and swelling, organ ischemia, endocarditis  Organ dysfunction: oliguria, jaundice, confusion, delirium or coma, purpura fulminans (rare, life threatening) 

Question 34

DIC diagnosis (labS)

Answer 34

CBC: thrombocytopenia peripheral blood smear: shistocytes PT/aPTT: prolonged D-Dimer: elevated Fibrinogen: decreased Specific factor assays: decreased

Question 35

Purpura Simplex

Answer 35

most common vascular hemorrhagic disorder, women more than men. increased bruising without known trauma. platelet count, tests of platelet function, blood coagulation, and fibrinolysis are normal. no treatment necessary

Question 36

Senile purpura

Answer 36

affects older people, especially those with history of sun exposure

Question 37

senile purpura s/sx:

Answer 37

s/sx: dark purple ecchymosis hands and forearms. medications like anticoagulants may worsen

Question 38

Henoch-Schönlein Purpura (HSP)

Answer 38

idiopathic inflammatory disorde. immune complexes involving IgA antibodies in smaller arterioles, venules, capillaries. commonly preceeded by acute viral or bacterial infection. self-limiting.

Question 39

HSP s/sx:

Answer 39

triad of symptoms: purpuric rash, abdominal pain, joint pain. glomerulonephritis in adutls (sequeleae)

Question 40

Polycythemia Vera

Answer 40

myeloproliferative disorder characterized by uncontrolled RBC production.

Question 41

polycythemia vera s/sx:

Answer 41

often asymptomatic, fatigue,weakness, dizziness, headaches, visual. itchiness after warm bath (aquagenic pruritus), red/warm/painful palms and soles possible digital ischemia. splenomegaly, thromboses.

Question 42

polycythemia vera labs

Answer 42

RBC, Hgb, and Hct elevated. neutrophils/ platelets may increase too. tx: phleobotomy

Question 43

secondary polycythemia

Answer 43

any elevation of Hb or Hct along with RBC incresae. no WBC or platelet increase. secondary to underlying conditions (smoking, cancers, tetralogy of fallot, chronic hypoxemia)

Question 44

Prothrombin Time (PT)

Answer 44

Prolonged in: Vitamin K deficiency Liver disease, including alcoholic hepatitis Biliary obstruction DIC Deficiency in factor I, II, V, VII, and X Warfarin (anti-coagulant) use

Question 45

prothrombin time (PT)

Answer 45

Measures the number of seconds it takes for a clot to form after reagents are added Reference range: 11-13 seconds Assess extrinsic and common pathways of the coagulation cascade Evaluates coagulation factors: I (fibrinogen), II (prothrombin), V, VII, and X Prothrombin is produced by the liver and its production depends on vitamin K intake and absorption

Question 46

International Normalized Ratio

Answer 46

Different reagents are used to assess PT, leading to different reference ranges. To standardize PT results across the world, International Normalized Ratio (INR) is established (calculated based on PT results). Used to monitor Warfarin (vitamin K antagonist) therapy. Warfarin is prescribed for people with DVT, PE, valve replacement, atrial fibrillation, post-MI, etc. to prevent inappropriate clotting Range should be between 2.0-3.0

Question 47

Activated Partial Thromboplastin Time (aPTT)

Answer 47

aPTT is a more sensitive version of PTT Measures the number of seconds it takes for a clot to form after reagents are added Reference range: 21-35 seconds Assess intrinsic and common pathways of the coagulation cascade Evaluates coagulation factors: all EXCEPT factor VII (assessed by PT) Does not become prolonged until one or more clotting factors are 70% deficient

Question 48

aPTT activated in:

Answer 48

Hemophilia A and B Vitamin K deficiency Liver disease, including alcoholic hepatitis DIC Heparin therapy / Warfarin therapy

Question 49

aPTT used to monitor...

Answer 49

heparin therapy

Question 50

mixing studies

Answer 50

patient's plasma mixed with 50:50 If clot forms (aPTT normalized/corrected), then it confirms a factor deficiency Especially deficiencies in factors VIII, IX, XI, XII and rarely VWF If clot fails to form (aPTT prolonged), then it confirms the presence of an inhibitor Heparin Antiphospholipid antibodies Coagulation factor specific inhibitors (often due to antibody development against specific factors)

Question 51

Fibrinogen

Answer 51

Normal reference range: 250-350 mg/dL Increased fibrinogen increases chances of clotting and coronary artery/cerebrovascular events. Also an acute phase reactant and rises with any condition that causes inflammation or tissue damage: cancer, inflammation/infection (RA, TB, pneumonia), glomerulonephritis, acute MI, stroke, pregnancy, eclampsia, etc. Non-specific so not used as such Decreased fibrinogen increases chances of hemorrhage after traumatic surgery. Low level seen in DIC, liver disease, severe malnutrition, cancer

Question 52

D-Dimer

Answer 52

A fibrin degradation product made by plasmin cleaving the crossed-linked fibrin mesh Normal range: < 250 ng/mL Screen for: DIC Venous thrombosis (PE, DVT) Acute MI D-Dimer is more specific for DIC compared to other fibrin degradation products.