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Name the two types of etiologies of hemolytic anemia and how they occur
1. Congenital: intrinsic defects of erythrocytes. 2. Acquired: Normal RBC but destroyed by autoimmune, infections, meds, and tumors
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What causes autoimmune secondary to erythrocyte damage in acquired hemolytic anemia
Cardiac valve protheses
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Where does destruction of RBC occur in hemolytic anemia
Macrophages in spleen
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What causes splenomegaly in Hemolytic Anemia
hyperplasia of phagocytes in spleen
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What is released as a result of decreased O2 in the blood that triggers bone marrow to make more (normoblasts) RBC
Erythropoetin
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What causes accumulation of hemosiderin (an iron containing pigment)?
phagocytosis of RBCs
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What organs does hemosiderin accumulate in?
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Name 5 types of acquired hemolytic anemias
- autoimmune
- traumatic
- infectious
- toxic
- physical
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Symptoms of Hemolytic anemia
- SOB
- Dizzy
- Fatigue
- weakness
- HA
- LEG ULCERS
- CARDIAC MALFUNCTIONS: dilation, valve insufficiency
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How is hemolytic anemia usually discovered
inadvertently to other conditions such as splenomegaly and gallstones
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What is done to prevent acute splenic sequesteration
splenectomy
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What two things must be addressed BEFORE splenectomy is considered
- Blood transfusions
- Managing hypovolemic shock
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Name 6 causes of leg ulcers s/c to Hemolytic anemia
- mechanical obstruction
- hypercoagualbility
- Venous insufficiency
- hemolysis-vascular dysfunction
- bacteria
- genetic
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Name 4 different neoplasms that fall under myeloproliferative disorders
- Chronic Myeloid Leukemia (CML)
- Polycythemia Vera
- Essential Thrombocythemia
- Primary myelofibrosis
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What age and gender is common for CML
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What has been one link to CML r/t environmental factors
radiation exposure
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What is the main pathologic feature of primary myelofibrosis
inc deposition of collagen in bone marrow by non-neoplastic fibroblasts
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What disease is INC granulocytes? Erythrocytes? Platelets?
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What gene is does CML occur on?
BCR on C22 that fuses with ABL1 on C9 resulting in abnormal fusion gene of BCR-ABL1 on C22
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What does translocation of C9 and C22 generate
Philadelphia chromosome
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What phase of CML is associated with leukocytosis with a left shift, ABSOLUTE basophilia, thrombocytosis, and blast count <5%
Chronic
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What phase of CML is associated with blast count of 10-20% with DISTINCT basophilia
Accelerated
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What phase of CML is associated with blast count >20%, Ph gene is seen in highest quantity, and is VERY difficult to manage
Blast phase/Crisis
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What mutation is common in the following 3 myeloproliferative disorders: PCV, ET, and PMF
tyrosine kinase JAK2 point mutation
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What mutation is common in both ET and PMF
MPA point mutation
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What percent of MPA point mutation is shown in ET and PMF
5-10% cases
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Name 2 CML morphological characteristics most common
- Leukocytosis >100,000
- Splenomegaly
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Name 3 MAIN morphological characteristics of PCV
- Residual Fat
- INC RBC progenitors
- extensive fibrosis
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What is the spent phase of PCV
extensive fibrosis
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What is the main morphologic characteristic of ET
Inc # and size of megakaryocytes
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What is the main morphological characteristic of PMF
Hypercellular progresses to HYPOcellular and ends in fibrosis
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Name s/s of CML
- Anemia
- Hypermetabolism
- fatigue/weak
- weight loss/anorexia
- splenomegaly
- bone or joint pain
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What causes bone/joint pain in CML
bone marrow expansion due to excessive WBC build up and presence of BCR-ABL1 gene
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S/s of PCV s/c to abnormal blood flow
- Low venous pressure circulation
- cyanosis
- HA/dizzy
- PRUIRITIS
- UE HTN
- BLEEDING
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3 MAJOR RISKS/COMPLICATIONS OF PCV
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What is the hallmark of myelofibrosis
obliterative marrow fibrosis
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S/S of ET
occlusion of small arterioles, thrombotic events
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What is erythromelalgia?
occlusion of small arterioles
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What 2 disorders is erythromelalgia associated with
PCV and ET
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What is it called when there is an inc in # of immature granulocytes released from bone marrow before they have matured into full WBC
Left shift
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How does bone marrow fibrosis ossuary in primary myelofibrosis
abnormal deposition of excessive collagen derived from fibroblasts
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Where was Philadelphia chromosome discovered
Philadelphia
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What factor mutation/absence is associated with hemophilia A and what genetic disorder is it
- Factor VIII
- X-linked recessive
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What ratio of the population and gender is common in Hemophilia A
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At what age is Hemophilia A usually diagnosed
6-12 months (crawling injuries)
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What 2 things prevent FVIII from being expressed
- Stop codons prevent expression
- Mutation makes it nonfunctional
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What does FVIII and other coagulation factors form and why is that important
FX, it is important because FX allows for formation of thrombin and fibrin. Without it, platelets can't stabilize and bleeding occurs
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What chromosome is FVIII located on
CX long arm
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What does activated FVIII form
tenase complex
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What does Tenase complex due when activated by FVIII
activated FX and begins clotting cascade
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What is the most common mutation of FVIII
inversion on intron 22
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S/s of hemophilia A
BLEEDING
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What is joint bleeding called
Hemarthrosis
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How is individuals with mild hemophilia A treated?
- Desmopressin (common)
- Vit K
- Herbs: Ginko and Tumeric
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What does desmopressin do for hemophilia A
releases additional clotting factors
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How can women experience mild sx of Hemophilia A if carriers
- If father is symptomatic Hemophilia A or
- Turner syndrome
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What happens if Hemophilia A needs surgery
Prophylactic bolus dose with IV drip of FVIII to maintain target level of 80-100%
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What is the ONLY CONFIRMED environmental factor of Acute Lymphoblastic Leukemia
high birth weight
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What gender, ethnicity, and socioeconomic class is most associated with ALL
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What is the HALLMARK of ALL
Chromosomal aberrations that result in dysregulation of normal T & B cell functioning
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What is most common gain of function mutation seen in T-ALL
NOTCH1 gene
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Why is NOTCH1 gene important
vital to T cell development
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What causes cancer r/t T-ALL
NOTCH1 overactivation leading to uncontrolled cell proliferation and growth
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What does marrow look like with ALL
hyper cellular filled with lymphoblasts
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What disease has Morphology of starry sky appearance
ALL
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Name 3 things present in 50-70% of T-ALL
- lympadenopathy
- splenomegaly
- mediastinal thymic mass
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What enzyme aids in distinguishing lymphoblasts from lymphocytes in ALL
TdT
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What does TdT express
lymphoblasts
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What appears on surface of mature B cells that is not present on lymphoblasts
immunoglobulins
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What causes s/s of ALL
- neutropenia
- thrombocytopenia
- anemia
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Name 5 complications of ALL
- Lymphadenopathy
- splenomegaly
- hepatomegaly
- testicular enlargement
- bone pain
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What nerve is commonly affected with ALL
Facial
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What can causes seizures and meningism in ALL
leptomeningeal involvement
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What is given prophylactically to prevent CNS involvement of ALL
IT chemo
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Name 2 common disorders that are inherited that cause thrombophilia
- Factor V Leiden
- Prothrmobin G20210A
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Name 3 less common inherited disorders of thrombophilia
- Deficiencies in:
- Protein C
- Protein S
- Anti-thrombin
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What is one common acquired disorder of thrombophilia
Antiphospholipid antibody syndrome
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What 2 things does elevated levels of homocysteine contribute to in thrombophilia
- arterial and venous thrombosis
- atherosclerosis
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What type of hemostasis occurs when platelets attach themselves to the damaged epithelium to form a thrombus
Primary
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What type of hemostasis occurs when there is a protein factor where fibrin strands are formed out of soluble fibrinogen
Secondary
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What occurs during the intrinsic pathway of Secondary hemostasis
Neg charged collagen that is damaged inside the endothelium activated FXII from its inactive state
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What occurs in the extrinsic pathway of secondary hemostasis
When injured epithelium cells come into contact with FXII
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What do endothelial cell manufactured prostacyclin and nitric oxide do
cause vasodilation and inhibit platelet activation
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Name causes of Acquired thrombophilia
- Stasis or vascular injury
- Oral contraceptives
- Cancer
- Advancing age due to reduced endothelial PG12 production
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What is most important cause of acquired thrombophilia
Stasis/Vascular injury
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How do oral contraceptives cause acquired thrombophilia
- inc hepatic synthesis of coag factors
- reduced anticoagulant synthesis
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Describe direction of thrombi between arterial and venous and where both lead to
- Arterial: retrograde (away)
- Venous: direction of blood flow
- Both lead to heart
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What are the laminations on thrombi viewed microscopically called
Lines of Zahn
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What do Lines of Zahn look like microscopically
pale platelet and fibrin deposits
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What are thrombi occurring in heart chambers or aortic lumen called
Mural thrombi
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What promotes cardiac mural thrombi
Abnormal myocardial contraction or endomyocardial injury
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What type of thrombi are normally occlusive
arterial
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What thrombi are known as red or stasis thrombi because they contain more enmeshed red cells
venous
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What is thrombi on heart valves called
vegetation
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S/S of thrombophilia
DVT MOST COMMON: pain, heaviness, cramps in LE, swelling, blue-red discoloration
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3 main life threatening sites of thrombi
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What 2 things are there an increased risk for s/c to Thrombophilia
- Acute Kidney Failure
- Pathologies in pregnancy
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What is a side effect of warfarin in patients with protein c deficiency and how is it counteracted (not bleeding)
- Skin necrosis
- Counteracted by overlapping with heparin
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