Heme Lecture 3

A collection of flashcards summarizing key points from the Hematology Lecture on platelet function and disorders.

What are the three phases of hemostasis?

1️⃣ Primary: Platelets adhere (via vWF & collagen), activate, and aggregate via fibrinogen. 2️⃣ Secondary: Coagulation cascade activates thrombin → converts fibrinogen → fibrin. 3️⃣ Tertiary: Fibrin cross-linking, clot stabilization, wound healing.

What is the normal platelet range and key thresholds?

150k–450k/µL; Surgical bleed risk <50k, Spontaneous bleed <10k.

What are classic bleeding findings in thrombocytopenia?

Petechiae, purpura, ecchymosis, mucosal bleeding, menorrhagia, ± intracranial hemorrhage.

What are the major mechanisms of thrombocytopenia?

● ↓ Production (marrow failure, drugs, nutrient deficiency) ● ↑ Destruction/consumption (ITP, HIT, TTP) ● Splenic sequestration ● Pseudo-thrombocytopenia.

What causes decreased production in thrombocytopenia?

Aplastic anemia, MDS, leukemia, chemo, alcohol, chloramphenicol, B12/folate deficiency.

What is the pathophysiology of Immune Thrombocytopenia (ITP)?

Autoantibodies (IgG) target platelet glycoproteins → splenic macrophage destruction.

What are common demographics for ITP?

1:10,000 people — half in children, often post-viral; adults (esp. women 20–40) → chronic form.

What is the presentation of ITP in children?

Acute (kids): post-viral, self-limited.

What is the presentation of chronic ITP in adults?

Chronic (adults): idiopathic, persistent thrombocytopenia ± mucosal bleeding.

What are the key symptoms of ITP?

Petechiae, gingival/nasal bleeding, menorrhagia, often well otherwise.

How is ITP diagnosed?

Diagnosis of exclusion. Bone marrow biopsy if >60 yrs, other cytopenias, no steroid response, or pre-splenectomy.

What are the treatment goals for ITP?

Maintain safe platelet count (>50k); avoid unnecessary transfusion.

What is first-line therapy for ITP?

Corticosteroids (Prednisone 1–2 mg/kg or Dexamethasone 40 mg × 4 days). IVIG for rapid rise (1 g/kg × 2 days).

What are refractory treatment options for ITP?

● Splenectomy (long-term control, give pneumococcal vaccine) ● Rituximab (anti-CD20) ● TPO agonists: Romiplostim (Nplate) SQ or Eltrombopag (Promacta) PO.

What is the pathophysiology of Heparin-Induced Thrombocytopenia (HIT)?

Heparin binds platelet factor 4 → immune complex forms → platelet activation → hypercoagulable state with thrombocytopenia.

What is the typical presentation of HIT?

Hospitalized patient, 5–10 days after heparin, platelet drop ≥ 50% from baseline. Bleeding rare; thrombosis common.

What diagnostic tests are used for HIT?

● 4Ts score (Thrombocytopenia, Timing, Thrombosis, oTher causes). ● PF4-heparin ELISA or functional assay.

What is the treatment for HIT?

● Stop all heparin. ● Avoid platelet transfusion. ● Start Argatroban (IV) or other direct thrombin inhibitor. ● Begin warfarin only after platelets >150k. ● Resolution ≈ 7 days.

What is the pathophysiology of Thrombotic Thrombocytopenic Purpura (TTP)?

Deficiency or inhibition of ADAMTS13, the enzyme that cleaves large vWF multimers → uncontrolled platelet aggregation → microvascular thrombi.

What is the classic pentad of TTP?

1️⃣ Microangiopathic hemolytic anemia (MAHA) 2️⃣ Thrombocytopenia 3️⃣ Fever 4️⃣ Renal failure 5️⃣ Neuro deficits.

What key laboratory findings are associated with TTP?

● Anemia with ↑ LDH/bilirubin, ↓ haptoglobin ● Schistocytes on smear ● Normal PT/PTT ● ADAMTS13 ↓ (send-out test).

How urgent is the treatment for TTP?

Plasma exchange immediately (mortality > 90% untreated). Also Prednisone, Rituximab, Caplacizumab.

What is sequestration-related thrombocytopenia?

Splenomegaly (portal HTN, cirrhosis, CHF, mono, malignancy) → platelet pooling.

What is pseudo-thrombocytopenia?

EDTA-induced platelet clumping during blood draw; repeat count in citrate tube.

What defines thrombocytosis?

450k/µL; risk of thrombotic/bleeding events if >1,000k/µL.

What is the difference between primary and secondary thrombocytosis?

● Primary: clonal overproduction (ET, PV, MDS, CML). ● Secondary: reactive (iron deficiency = #1, malignancy, infection, post-splenectomy).

What are the features of primary thrombocytosis?

Vasomotor symptoms (headache, vision changes, acral paresthesia) + ↑ thrombosis/bleeding risk.

What are Myeloproliferative Neoplasms (MPN)?

Clonal proliferations of hematopoietic stem cells → ↑ production of one or more blood lines. Includes Polycythemia Vera (PV), Essential Thrombocythemia (ET), and CML.

What is the pathophysiology of Polycythemia Vera (PV)?

JAK2 mutation (~95%) → uncontrolled RBC, WBC, platelet production.

What are diagnostic clues for Polycythemia Vera (PV)?

Hgb > 18.5 ♂ / 16.5 ♀, ↓ EPO (if EPO ↑ = secondary polycythemia).

What are common symptoms of Polycythemia Vera (PV)?

Headache, visual changes, pruritus after bathing, plethora, tinnitus, HTN, thrombosis, hepatosplenomegaly.

What is the treatment for Polycythemia Vera (PV)?

● Phlebotomy until Hct < 45% ● ASA 81 mg daily ● Hydroxyurea / Interferon-α (myelosuppression) ● Stem cell transplant (only curative) ● Can progress to myelofibrosis or AML (3–10%).

What are the lab findings in Essential Thrombocythemia (ET)?

Platelets > 450k, JAK2 ±, possible acquired vWF syndrome if >1,000k.

How is risk stratification performed in Essential Thrombocythemia (ET)?

● High: Age > 60 + thrombosis + JAK2 + ● Intermediate: Age > 60, no JAK2, no thrombosis ● Low/very low: Age < 60 ± JAK2, no thrombosis.

What are symptoms of Essential Thrombocythemia (ET)?

Usually asymptomatic, may have headache, syncope, chest pain, livedo reticularis, splenomegaly.

What is the treatment for Essential Thrombocythemia (ET)?

● ASA 81 mg (vasomotor relief, prevent thrombosis) ● Hydroxyurea, Anagrelide (lower platelet production) ● Treat secondary cause if reactive.

When should you transfuse RBCs?

Generally Hgb < 7 g/dL (or < 8 if cardiac disease) + symptomatic anemia.

How much does each unit of RBCs increase Hgb and Hct?

Each unit ↑ Hgb ≈ 1 g/dL and Hct ≈ 3%.

What are the ABO blood group basics?

● A: A antigen, anti-B antibodies ● B: B antigen, anti-A antibodies ● AB: both antigens, no antibodies ● O: no antigens, anti-A/B antibodies.

What is the significance of the Rh system?

Rh (+) = D antigen present. Rh (–) exposed to Rh (+) forms antibodies → hemolysis in future transfusions or pregnancy.

How is hemolytic disease of the newborn prevented?

RhoGAM (anti-D Ig) at 28 weeks & postpartum for Rh(–) mothers.

What are the uses and notes for PRBCs?

Anemia; ↑ O₂ delivery.

What are the notes for leukodepleted blood products?

↓ CMV, HLA alloimmunization.

What are the uses for washed RBCs?

Removes 99% plasma (for allergy hx).

What are the uses for frozen RBCs?

Long-term rare type storage.

What is the indication for irradiated / CMV-negative blood products?

Immunocompromised / BMT patients.

What is the use for platelet transfusions?

Thrombocytopenia / bleeding prevention.

What is fresh frozen plasma (FFP) used for?

Coagulation factor replacement.

What is cryoprecipitate used for?

Fibrinogen / Factor XIII deficiency.

What causes a hemolytic transfusion reaction?

ABO incompatibility → complement-mediated intravascular hemolysis.

What are the symptoms of a hemolytic transfusion reaction?

Fever, chills, chest/back pain, hypotension, sense of doom.

What is the treatment for a hemolytic transfusion reaction?

Stop transfusion, send labs, aggressive IV fluids.

What causes an allergic transfusion reaction?

Reaction to donor plasma proteins → urticaria, bronchospasm.

What is the treatment for an allergic transfusion reaction?

Stop transfusion; diphenhydramine, acetaminophen, corticosteroids.

What is the risk associated with infectious contamination of blood products?

Platelet products at higher risk.

What are the symptoms of gram-positive infectious contamination?

Mild fever.

What are the symptoms of gram-negative infectious contamination?

Sepsis/DIC.

What is the treatment for infectious contamination?

Broad-spectrum antibiotics, culture products.

What is Transfusion-Related Lung Injury (TRALI)?

Non-cardiogenic pulmonary edema within 24 h; donor anti-leukocyte antibodies.

What is the treatment for TRALI?

Supportive.

What is transfusional hemosiderosis?

Iron deposition in liver, heart, pancreas, endocrine glands from repeated transfusions (> 50–100 units).

What are symptoms of transfusional hemosiderosis?

Fatigue, skin pigmentation, DM, CHF, liver disease.

What are the lab findings for transfusional hemosiderosis?

Ferritin > 1000 ng/mL, Liver Fe > 7 mg/g.

What is the treatment for transfusional hemosiderosis?

Chelation (Deferoxamine, Deferasirox).

What causes hereditary hemochromatosis?

Autosomal recessive HFE gene (C282Y, H63D) mutation → ↑ intestinal iron absorption.

What are key findings in hereditary hemochromatosis?

Fatigue, arthralgia, hepatomegaly, skin bronzing, diabetes, cardiomyopathy, arrhythmia.

What labs are associated with hereditary hemochromatosis?

↑ Ferritin, serum iron, LFTs, confirm with HFE genetic test or liver biopsy.

What is the treatment for hereditary hemochromatosis?

Therapeutic phlebotomy, ± iron chelation if needed.

What is the summary of ITP?

ITP = autoimmune platelet destruction → steroids/IVIG/splenectomy.

What is the summary of HIT?

HIT = heparin + PF4 antibodies → Argatroban, no platelets.

What is the summary of TTP?

TTP = ADAMTS13 ↓ → plasma exchange + steroids ± Rituximab.

What is the summary of Polycythemia Vera (PV)?

PV = JAK2 +, low EPO → phlebotomy + ASA.

What is the summary of Essential Thrombocythemia (ET)?

ET = ↑ platelets → ASA + hydroxyurea.

What is the summary of Transfusion-Related Lung Injury (TRALI)?

TRALI = non-cardiogenic pulmonary edema → supportive.

What is the summary of hemochromatosis?

Hemochromatosis = C282Y mutation → phlebotomy.