Heme Patho pt. II

Anemia

• Definition: decreased number of RBCs, hemoglobin, or oxygen-carrying capacity of blood

• Major Causes: ↓ RBC production, blood loss (acute or chronic), ↑ RBC destruction (hemolysis)

• Clinical Result: tissue hypoxia, fatigue/weakness/dyspnea/pallor

• RBC characteristics:

  • Cell size (MCV): microcytic, normocytic, macrocytic

  • Hemoglobin content (MCHC): normochromic, hypochromic

Anemia - types

1. Blood loss anemia

2. Iron deficiency anemia

3. Pernicious anemia

4. Anemia of chronic diseases

5. Sickle cell anemia

1. Blood loss anemia

• Classification:

  • Usually normocytic, normochromic

  • RBC production is normal → blood is being lost

• Acute Blood Loss:

  • Hemorrhage or trauma

  • Severity depends on rate & amount of blood loss

  • Significant blood loss can lead to hypovolemia, shock, and death

• Chronic Blood Loss:

  • Slow, ongoing bleeding (ex/ GI ulcer, colon cancer, heavy menstrual bleeding)

  • Symptoms develop gradually

  • May progress to iron deficiency anemia

2. Iron deficiency anemia (most common worldwide)

• Classification:

  • Microcytic, hypochromic anemia

    • Small RBCs with decreased hemoglobin

• Common Causes:

  • Inadequate dietary intake

  • Increased iron requirements (growth, pregnancy)

  • Impaired GI absorption

  • Chronic blood loss (most common cause in adults)

• Clinical Manifestations:

  • Fatigue, weakness, dyspnea, pallor

  • Brittle, spoon-shaped nails (koilonychia)

  • Cheilosis (fissures in mouth) and stomatitis

  • Glossitis

  • Dysphagia

3. Pernicious anemia

• Classification:

  • Macrocytic, normochromic anemia

  • Large RBCs due to impaired DNA synthesis

• Cause:

  • Vitamin B12 deficiency

  • Most commonly caused by autoimmune gastritis

    • Loss of intrinsic factor → impaired B12 absorption

• Clinical Manifestations:

  • Fatigue, weakness

  • Smooth, beefy-red tongue (glossitis)

  • Paresthesias (numbness/tingling)

  • Difficulty walking, loss of balance (ataxia)

  • Neurologic damage may be irreversible

Distinction b/w iron deficiency & pernicious anemia

• Iron anemia (iron deficiency) = no neuro symptoms

• Pernicious anemia (B12 deficiency) = neuro symptoms

4. Anemia of chronic disease (inflammation)

• Classification:

  • Usually normocytic, normochromic

  • May become microcytic, hypochromic over time

• Associated Conditions:

  • Chronic infections

  • Autoimmune diseases

  • Cancer

  • Chronic inflammatory disorders

• Pathophysiology:

  • Chronic inflammation suppresses RBC production

  • Decreased erythropoietin (EPO) response

  • Iron becomes trapped in storage sites

  • Iron is present, but cannot be used

    • **Iron utilization problem, not iron deficiency problem**

• Clinical Manifestations:

  • Usually mild & gradual → fatigue, weakness, pallor

• Treatment:

  • Manage underlying disease, rather than just replacing iron

5. Sickle cell anemia

• Classification:

  • Hemolytic anemia

  • Usually normocytic, normochromic

• Pathophysiology:

  • Inherited disorder causing abnormal hemoglobin (HbS)

  • Low oxygen levels trigger RBC sickling

  • Sickled cells are rigid and fragile

• Results in:

  • Hemolysis (RBC destruction)

  • Vaso-occlusion (blocked blood vessels)

• Complications:

  • Acute chest syndrome

  • Stroke

  • Organ damage

  • Splenic dysfunction

• Clinical manifestations:

  • Chronic anemia

  • Fatigue & pallor

  • Painful vaso-occlusive crises

  • Delayed growth & development

  • Increased risk of infection

Anemia - comparison table

Start here → don’t focus all studying on it! (it doesn’t include everything)

Blood malignancy - types

1. Polycythemia Vera

2. Leukemia

3. Lymphoma

   1. Includes Lymphadenopathy

1. Polycythemia Vera

• What Is It?

  • Myeloproliferative blood cancer

  • Bone marrow produces too many RBCs

  • WBCs and platelets may also be elevated

• Pathophysiology

  • ↑ RBC mass

  • ↑ Hematocrit

  • ↑ Blood viscosity ("thick blood")

• Clinical Manifestations

  • Headache

  • Dizziness

  • Blurred vision

  • Fatigue

  • Ruddy/red complexion

  • Splenomegaly

  • Aquagenic pruritus (itching after warm water)

• Major Complication: thromboembolism (blood clots)

• Treatment: therapeutic phlebotomy, low-dose aspirin

2. Leukemia - overview

• What Is It?

  • Cancer of the bone marrow and blood

  • Uncontrolled proliferation of abnormal WBCs

  • Leukemic cells crowd the bone marrow

• Consequences of Bone Marrow Crowding

  • ↓ RBC production → Anemia

  • ↓ Platelet production → Bleeding

  • ↓ Functional WBCs → Infection

• Common Manifestations

  • Fatigue

  • Fever

  • Recurrent infections

  • Easy bruising or bleeding

  • Lymphadenopathy

  • Splenomegaly

  • Night sweats

• Treatment: chemotherapy, radiation therapy, stem cell transplant, immunotherapy, supportive care

2. Leukemia - classifications

• Acute Leukemias

  • Rapid onset and progression

  • Immature "blast" cells present (WBCs)

  • Require prompt treatment

  • ALL: Acute Lymphocytic Leukemia

    • Most common childhood leukemia

  • AML: Acute Myelogenous Leukemia

    • Most common acute leukemia in adults

• Chronic Leukemias

  • Slower progression

  • More mature abnormal cells

  • May be asymptomatic initially

  • CLL: Chronic Lymphocytic Leukemia

    • Most common adult leukemia

  • CML: Chronic Myelogenous Leukemia

    • Most common middle aged adult Leukemia

3. Lymphoma - symptoms

• What Is It?

  • Cancer arising from malignant lymphocytes in the lymphatic system

  • Often begins in lymph nodes but may occur in other lymphoid tissues

  • Two major categories:

    • 1. Hodgkin Lymphoma (HL) → begins in 1 lymphnode group & spread in orderly fashion to the next to the next

      • Reed-Sternburg cells

    • 2. Non-Hodgkin Lymphoma (NHL) → unpredictable, outside lymph nodes

• Hallmark Finding: Lymphadenopathy

  • Painless enlarged lymph nodes

  • Most common presenting sign

  • May be localized or generalized

  • Enlarged lymph nodes do not always indicate cancer (may occur with infection or inflammation)

• Clinical Manifestations

  • Fatigue

  • “B Symptoms”

    • Fever without infection, drenching night sweats, unexplained weight loss, splenomegaly

• Risk Factors

  • Immunosuppression (HIV/AIDS, organ transplantation), autoimmune disorders, certain viral infections (EBV)

• Treatment: chemotherapy, radiation therapy, stem cell transplant, CAR-T therapy (selected patients)

3. Lymphoma - types chart

3. Lymphoma - lymphadenopathy visual

Blood malignancies - comparison table

Clotting disorders - types

1. Immune Thrombocytopenia

2. Heparin Induced Thrombocytopenia

3. Disseminated Intravascular Coagulation

Thromboembolic disorders (blood clots)

• Key Terms

  • Thrombus: A blood clot that remains attached to a vessel wall

  • Embolus: A clot (or fragment of a clot) that travels through the bloodstream

• Virchow's Triad: why clots form

  • Endothelial Injury: surgery, trauma, inflammation, etc.

  • Hemodynamic Stasis: immobility, atrial fibrillation, venous stasis, etc.

  • Hypercoagulability: cancer, pregnancy, genetic clotting disorders, etc.

• Why do we care?

  • A clot that travels can block blood flow & cause…

    • DVT (deep vein thrombosis), PE (pulmonary embolism), stroke, myocardial infarction

1. Immune Thrombocytopenia (ITP)

• Platelet destruction that exceeds production

• 70% are preceded by viral diseases (CMV, EBV, Parvovirus, or respiratory tract infections)

• Manifestations: petechiae, purpura, bruising, progresses to major bleeding

• Prognosis = excellent, with 80%-90% regaining normal platelet counts within 6 months after onset

• Treatment: meds to subdue the immune system (corticosteroids, IVIG, Immunosuppressive therapy)

• **Bleeding disorder**

2. Heparin Induced Thrombocytopenia (HIT)

• What Is It?

  • Immune-mediated adverse reaction to heparin (or enoxaparin)

  • Antibodies activate platelets

• What Happens?

  • 1. Heparin exposure

  • 2. Platelets become activated

  • 3. Abnormal clot formation occurs

  • 4. Platelets are consumed

  • 5. Platelet count falls (>50% decrease)

• Hallmark Findings

  • Platelet count ↓ more than 50%

  • Usually develops 5-10 days after starting heparin

  • Positive HIT antibody test

• Major Concern: THROMBOSIS (clotting), not bleeding

  • DVT, PE, stroke, MI

• Treatment: stop all heparin products immediately, start alternative anticoagulant

• **Clotting disorder** → platelets are low b/c they’re making clots

3. Disseminated Intravascular Coagulation (DIC)

• What Is It?

  • Life-threatening activation of the clotting cascade (not just activating platelets)

  • Usually triggered by another condition (sepsis/infection, trauma, cancer, obstetric emergencies)

• What Happens?

  • Widespread clot formation in small vessels

  • Organ blood flow decreases

  • Platelets and clotting factors are consumed

  • Patient develops bleeding

• **BOTH clotting and bleeding disorder**

3. DIC - manifestations

• Signs & Symptoms (unexpected bleeding)

  • Oozing from IV sites and wounds

  • Petechiae, purpura, ecchymoses

  • Bleeding from gums or mucous membranes

  • Symmetric cyanosis of fingers and toes

  • Organ dysfunction

  • Thrombocytopenia

• Diagnosis: clinical picture + coagulation studies (lab data)

• Treatment: treat the underlying cause, blood products as needed, organ support (dialysis, ventilator, etc.)

Coagulation disorders - comparison table

Summary of the major difference b/w ITP, HIT, & DIC

• ITP destroys platelets

• HIT activates platelets

• DIC consumes platelets & clotting factors