aquired autoimmune HA

Question 1

what is autoimmune HA

Answer 1

occurs when your immune system mistakes red blood cells as unwanted substances. As a result, your body produces antibodies that destroy red blood cells, which can lead to a low amount of red blood cells (known as anemia).

Question 2

what is the most common type of AIHA

Answer 2

warm autoimmune hemolytic anemia (80% of cases)

Question 3

what type of autoantibodies are in warm hemolytic anemia

Answer 3

IgG (girls= hot)

Question 4

what happens in warm autoimmune HA

Answer 4

-Caused by autoantibodies that react with self RBCs at body temperature (37o)

• Leads to sequestration in the spleen > extravascular hemolysis ( the igG-coated RBCs are then
  engulfed/removed by reticule-endothelial macrophages of the spleen leading to splenomegagly)

Question 5

causes of warm autoimmune HA

Answer 5

• May be primary/idiopathic or secondary (50-60% of cases) to:
  1. Chronic lymphocytic leukemia (CLL)
  2. Lymphoma
  3. Systemic lupus erythematosus (SLE)
  4. Drugs: penicillin, alpha methyldopa, rifampin, phenytoin

Question 6

what is the blood film in warm autoimmune HA

Answer 6

• Macrophages partially phagocytose these RBCs, leading to the formation of spherocytes (small, dense red cells).

Question 7

direct coombs test in WAIHA

Answer 7

• Positive IgG (confirms warm AIHA)
positive complemet

Question 8

tx of warm AIHA

Answer 8

1. Glucocorticoids (prednisone): best initial therapy; remission in 80% reduce antibody production
2. Recurrent episodes respond to splenectomy. ( for patient does not respond to glucocorticoids)
3. if not controlled > rituximab(anti-cd20antibody) ,immunosuppression: azathioprine, cyclophosphamide, or cyclosporine. (For patient does not respond to splenectomy)
4. Severe, acute hemolysis not responding to prednisone > IVIg

Question 9

what is diff btwn warm and cold autoimmune in terms of temp

Answer 9

-Warm AIHA is caused by IgG antibodies that attack RBCs at normal body temperature.

-Cold agglutinins are IgM autoantibodies that react with self RBCs at low temperatures (4 to 23)

Question 10

what happens in cold agglutinin disease

Answer 10

• IgM fixes complement (C3b and C5b-C9) onto the RBC surface.

• Intravascular hemolysis occurs when the membrane attack complex (MAC) forms and lyses RBCs.

• Some extravascular hemolysis occurs when C3b-coated RBCs are removed by macrophages in the liver (Kupffer cells).

Question 11

what are causes of cold AIHA

Answer 11

May be primary (esp. in elderly) or secondary to:

1. Infection (Mycoplasma pneumoniae, Epstein-Barr virus, CMV)
2. Lymphoid or plasma cell malignancies (B-cell lymphomas, CLL, Waldenström macroglobulinemia)

Question 12

what are symptoms in cold agglutinis

Answer 12

May present as cold-induced symptoms
(acrocyanosis, livedo reticularis, Raynaud phenomenon, numbness/mottling of the nose/ears/fingers/toes) or as hemolysis (may range from mild to severe)

Question 13

what are investigation of cold agluttinins

Answer 13

1. Direct Coombs test: positive only for complement
2. Cold agglutinin titer: most accurate test (positve)
3. Blood film: red cell agglutination at room temperature (RBC aggregates)

Question 14

what is paroxysmal nocturnal hemoglobinuria

Answer 14

RBCs have proteins called CD55 and CD59, which protect them from being destroyed by the complement system (a part of the immune system that helps fight infections).
• In PNH, a genetic mutation in the PIGA gene causes RBCs to lose CD55 and CD59, leaving them unprotected.
• As a result, the immune system’s complement attacks and destroys RBCs (intravascular hemolysis).

Question 15

PIGA gene required for synthesis of what

Answer 15

GPI protein on cell surface

GPI anchors glycoproteins on erythrocyte surface, protecting cell from lysis by attenuating activity of complement

Question 16

features of PNH

Answer 16

•Hemolysis (episodic dark urine
•Cytopenias– may present withpancytopenia or iron deficiency anemia

• Venous thrombosis esp. in unusual places (hepatic, portal, cerebral, abdomen➡ bowel necrosis)

Question 17

most accurate test of PNH

Answer 17

decreased level of CD55 and CD59

Question 18

what is myeloproliferative disorder

Answer 18

-Myeloproliferative disorders (MPDs) are a group of diseases where the bone marrow produces too many blood cells (red cells, white cells, or platelets).

-These disorders happen due to genetic mutations that cause uncontrolled cell growth.

Question 19

Types of Myeloproliferative Disorders & What Happens

Answer 19

1. Polycythemia Vera (PV) – Too Many Red Blood Cells
2. Essential Thrombocythemia (ET) – Too Many Platelets
3. Primary Myelofibrosis (PMF) – Scarred Bone Marrow
4. Chronic Myeloid Leukemia (CML) – Too Many White Blood Cells

Question 20

all disorders of MPD lead to what

Answer 20

AML

Question 21

what is the mutation in Polycthemia vera

Answer 21

JAK 2 gene mutation

Question 22

presentation of Polycthemia vera

Answer 22

1. General Symptoms (Due to High RBC Count & Thick Blood)
   • Headaches, dizziness, blurred vision (due to poor circulation)
   • Fatigue & weakness (less oxygen delivery despite high RBCs)
   • Shortness of breath
2. Clotting & Circulation Problems
   • Increased risk of blood clots (thrombosis) → Strokes, heart attacks, deep vein thrombosis (DVT), pulmonary embolism
   • Erythromelalgia → Burning pain & redness in hands/feet due to poor circulation
   • High blood pressure (hypertension)
3. Skin Symptoms
   • Itching after a hot shower (aquagenic pruritus) – Due to excess histamine release from increased mast cells
   • Reddish/purplish skin (plethora), flushed face
4. Splenomegaly (Enlarged Spleen)
   • Early satiety (feeling full quickly)

Question 23

what is gaisbocks syndrome

Answer 23

-Classically described as polycythemia in tense/anxious patient with hypertension, no splenomegaly and reduced plasma volume.

-Usually middle-aged obese man, smoker, high alcohol intake. Normal Hct but low plasma volume.

Question 24

what is primary meyelofibrosis

Answer 24

-increased fibrous tissue in the bone marrow replacing the normal hematopoietic activity

-Initially panmyelosis > with disease progression pancytopenia with BM fibrosis

Question 25

symptoms in primary myelofibrosis

Answer 25

• Anemia (Low RBCs) → Fatigue, weakness, pale skin, shortness of breath • Low WBCs → Increased infections • Low Platelets → Easy bruising, bleeding (nosebleeds, gum bleeding) Big Spleen (Splenomegaly) – A Key Feature • Night sweats, weight loss, fever (due to high inflammatory cytokines)

Question 26

Primary myelofibrosis mutation in what

Answer 26

• A genetic mutation (JAK2, CALR, or MPL) causes abnormal stem cells in the bone marrow to overproduce fibroblasts (cells that create scar tissue). (jak 2 50%)

Question 27

blood film in PF woukd show

Answer 27

leucoerythroblastic picture (myelocytes, teardrop RBCs, immature nucleated RBCs)

Question 28

what chromosome is absent in Primary myelofibrosis

Answer 28

philadelphia

Question 29

what is mutation in essential thrombocytopenia

Answer 29

Jak2 mutation (40-50%) causes megakaryocytes (the cells that produce platelets) to overproduce platelets.

Question 30

when do u treat ET

Answer 30

Only treated if age > 60 & has thrombosis or platelets > 1.5 million

Question 31

what happens in chronic myeloid leukemia

Answer 31

• So in chronic myeloid leukemia there is increase in WBCs {especially the granulocytes} so there is leukocytosis

Question 32

how can CML be misdiagnosed

Answer 32

If Someone has infection, he will also have increase WBCs so CML can sometimes be miss diagnosed with normal infection.

Question 33

Why Does CML Happen? (The Root Cause)

Answer 33

• A genetic mutation creates the Philadelphia chromosome (t[9;22]), which forms the BCR-ABL fusion gene. • This gene produces an abnormal protein (tyrosine kinase) that causes uncontrolled growth of WBCs, leading to leukemia.

Question 34

symptoms of CML in 3 clinical phases

Answer 34

1. Early (Chronic Phase – Often Asymptomatic) 85% diagnosed here • Fatigue, weakness • Weight loss • Night sweats • Enlarged spleen (left upper abdominal fullness) 2. Accelerated Phase (More Symptoms Appear) • Increased WBCs and worsening anemia • Easy bruising or bleeding • More frequent infections 3. Blast Crisis (Aggressive, Like Acute Leukemia) • Severe anemia → Extreme fatigue • Bone pain • Fever, infections • High blast cells (>20%) in blood → Very dangerous

Question 35

How is CML Diagnosed?

Answer 35

• Complete Blood Count (CBC) → Very high WBCs, low RBCs • Peripheral Blood Smear → Shows immature WBCs • Genetic Testing → Philadelphia chromosome (BCR-ABL fusion gene) • Bone Marrow Biopsy → Confirms diagnosis & stage

Question 36

tx of CML

Answer 36

1. Tyrosine Kinase Inhibitors (TKIs) – First-Line Treatment • Imatinib (Gleevec), Dasatinib, Nilotinib • These drugs block the BCR-ABL protein and stop WBC overproduction 2. Chemotherapy (If Blast Crisis Occurs) • If CML turns aggressive, chemo is used like in acute leukemia 3. Bone Marrow Transplant (Only for Severe Cases)

Question 37

what is myelodysplastic syndrome

Answer 37

is a bone marrow disorder where the bone marrow does not produce healthy blood cells properly. This leads to low blood counts (cytopenias) and, in some cases, can progress to acute myeloid leukemia (AML).

Question 38

Why Does MDS Happen? (The Root Cause)

Answer 38

• Bone marrow stem cells become damaged due to genetic mutations. • These damaged stem cells cannot make normal red blood cells (RBCs), white blood cells (WBCs), or platelets. • Instead, the bone marrow makes abnormal (dysplastic) cells that often die early.

Question 39

genetic testing in myelodysplastic syndrome in 50% of people

Answer 39

5q deletion