4. Anemia, Bleeding, Thrombosis

HOMER U. CO, M.D.

Hematology Lectures

HOMER U. CO, M.D.

AnemiaA Clinical Approach

Objectives

To discuss important physiology related to anemia Basic Red Blood Cell physiology Compensatory mechanisms

To provide a clinical context for studying anemia Features in history: what to ask Features in physical examination: what to look for Laboratory work-up algorithm

PHYSIOLOGY

Anemia

Basic Red Blood Cell Physiology

Compensatory Mechanisms

Increased cardiac outputIncreased respiratory driveShunting of blood away from the ff:

Kidneys Skin Gut

Compensatory Mechanisms

Increased 2,3 DPG in RBCs

HISTORY AND

PHYSICAL EXAMINATION

Anemia

History

Duration Acute (recent)

Sudden drops in Hgb levels Etiologies? Clinical presentation?

Sub-acute-chronic (weeks to months) Slow and progressive/plateau drop in Hgb Etiologies? Clinical presentation?

Key Points

Acute massive hemorrhage – symptoms due to hypovolemia Tachycardia Postural Hypotension Cold-clammy extremities

Chronic blood loss - symptoms due to decreased oxygen carrying capacity of blood Easy fatigability Shortness of breath

History

Other unusual signs/symptoms Due to other cell-line problem (WBC/Platelet problem)

Bleeding/petechiae/hematomas Fever

Inflammation Joints, skin, muscle, etc.

Other chronic systemic/organ dse Liver, kidneys, spleen, etc.

Medical History Co-morbid conditions Medication use Nutrition status

Key Points

Isolated RBC problem Iron deficiency RBC destruction RBC production problem

With WBC/Platelet problem Hematologic malignancy Bone marrow function

Systemic problem Chronic inflammation – CTDs, other rheuma condition Liver, kidney diseases

LABORATORY WORK UP

Anemia

Basic Concepts

Three (3) Functional Classification of Anemia Bone marrow production defects

hypoproliferative Red cell maturation defects

Ineffective erythropoiesis Decreased red cell survival

Blood loss/ hemolysis

Anemia Algorithm

CLINICAL SCENARIOSWHAT TO ASK AND LOOK FOR

Anemia

Scenario 1

A 75 year old Male presents at the ER with pallor and hypotension. He has 3 days of melena and generalized body weakness.

Scenario 2

A 45 year old female consults you at the clinic for pallor. She seems well except for easy fatigability in performing the usual household chores.

Scenario 3

A 35 year old male consults at the clinic for elevated blood pressure. He has had on and off bipedal edema and easy fatigability. He has also lost some weight due to anorexia since a month ago. He looks pale with white nailbeds and palms.

Scenario 4

A 23 year old female presents with prolonged and heavy menstrual bleeding and pallor.

HOMER UY CO, M.D.

Platelet and Coagulation Disorders

Objectives

To discuss important physiology related to bleeding and thrombosis Platelets, coagulation and anti-coagulation factors

To provide a clinical context for studying bleeding and thrombosis Features in history: what to ask Features in physical examination: what to look for Laboratory work-up algorithm

PHYSIOLOGY

Bleeding and Thrombosis

Platelet Plug Formation

Fibrin Clot Formation

Coagulation Factors

Anti-thrombotic Mechanisms

Fibrinolytic System

Causative Factors

Bleeding disorders (Inherited or Acquired) Platelet disorders Coagulation factor deficiency

Thrombotic disorders (Inherited or Acquired) Protein C/S deficiency Factor V Leiden Anti-thrombin deficiency Other Risk Factors

HISTORY AND PHYSICAL EXAMINATION

Bleeding and Thrombosis

History

Bleeding Chronicity

Inherited vs acquired Sites of bleeding

Mucosal/superficial vs deep tissue/joints Co-morbid medical conditions

Renal/hepatic failure/sepsis Exposures

Drug – antiplatelets, anti-coagulants Food/supplements

Spontaneous or Provoked Severity of underlying bleeding disorder

History

Thrombosis Predisposing conditions

Malignancy Immobilization Pregnancy Medications

Past occurences

LABORATORY WORK UP

Bleeding and Thrombosis

Bleeding Parameters

Platelet countBleeding timeProthrombin Time (ProTime) / INRActivated Partial Thromboplastin Time (aPTT)

Thrombophilic tests

Protein C/ Protein S“APAS” tests

Anti-phospholipid anti-body tests (anti-cardiolipin) Dilute Russell Viper Venom Test (dRVVT) aPTT with mixing (“Lupus” anti-coagulant)

Specific factor assaysScreen for malignancy (if likely)

CLINICAL SCENARIOSWHAT TO ASK AND LOOK FOR

Bleeding and Thrombosis

Scenario 1

A 24 year old female presents with a 2 week history of petechial and purpuric rashes over the extremities and gum bleeding.

Scenario 2

A 32 year old female develops a painful and swollen right leg. She is perfectly well before. She has no history of recent trauma, prolonged air travel nor immobilization.

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