Hematology

Mohamad H Qari, MD, FRCPA

Hematology

Cellular ComponentsComponents of BloodRed Blood CellsWhite Blood Cells Inflammatory processCoagulation

Blood TypingClotting disorders

Hematology

SpleenSpleen

KidneysKidneys

LiverLiverBoneMarrowBone

Marrow

BloodBlood

HematopoieticSystem

HematopoieticSystem

Hematopoeisis

Three developmental periods Mesoblastic

Blood islands of yolk sac Primarily RBC production Embryonic hemoglobin produced

Hepatic At 6 weeks cell production in liver Fetal hemoglobin produced Spleen, thymus, lymph nodes also active prod.

Myeloid At 5th month Bone Marrow becomes site of prod. Liver & spleen now Extramedullary Hemoglobin A (22)

Requirements For Hematopoiesis

Stem Cells

Growth Factors

Microenviroment

Stem Cell theory

Pluripotent stem cell originator of all cells Gives rise to cells committed to specific

development Research supporting the theory PHSC has self-maintaining ability Committed cells differentiate continuously/ No

Reverse Flow

Stem cells in Research

Pluripotent cells derived from: Cell mass of embryos at blastocyst stage (IVF) Fetal tissue from terminated pregnancy

Application Identification of factors of cellular decision-making Development and testing of drugs Generation of cells and tissue for therapy

Cytokines & Growth Factors

Cytokines stimulate or inhibit Prevent apoptosis Colony-Stimulating Factors produced by

many different cells Interleukins numbered according to discovery

Components of Blood

Plasma Transport mechanism

90-92% water. 6-7% proteins 2-3%

Fats Carbohydrates

(glucose) Electrolytes Gases (O2, CO2) Chemical messengers

Plasma Components

Other3%

Protein7%

Water90%

Cellular Components

Pluripotent Stem Cell

Myeloid Multipotent Stem Cells

Common LymphoidStem Cells

Unipotent Progenitors

BasophilsEosinophilsNeutrophilsMonocytes

Lymphocytes

ErythrocytesThrombocytes

Erythropoietin

WBC’sRBC’s

Platelets

Components of Blood

Red Blood Cells Erythrocyte

Hemoglobin – O2 bearing molecule

Comprised of 4 subunits:

• Globin (binds to 1 O2 molecule)

• Heme (iron) 100% saturation = 4

globin subunits carrying O2

• Each gram of hemoglobin = 1.34 ml O2

Cellsalive.com

Blood Products and Blood Typing

Blood TypesAntigens

A, B, AB, ORh factor

Rh+ = ~85%Rh- = ~15%

Blood transfusion

Components of BloodRed Blood Cells (cont.) Oxygen Transport

Oxy-hemoglobin dissociation curve

2,3-DPG

Components of Blood

White Blood Cells (Leukocytes) Margination Phagocytosis

White Blood Cells (Leukocytes) Margination Phagocytosis

The macrophage is using its internal cytoskeleton to envelop cells of the fungus Candida albicans.

Components of Blood

Leukocytes (cont.)White Blood Cell CountLeukopoiesis

Granulocytes Neutrophil Basophil Eosinophil

MonocytesLymphocytes

Human Neutrophil: Phagocytosis of Strep pyogenes

Components of BloodLeukocytes (cont.) Immunity

Subpopulation of lymphocytes known as T cells and B cells T cells develop cellular immunity. B cells produce humoral immunity

Components of Blood

Inflammatory Process MAST CELLS.

Immunoglobulin E antibody IgE,  

Antigens Antigens stick to the mast cell IgE

antibodies, causing granules in the mast cell to fire their contents into the surrounding tissue.

This releases a host of inflammatory materials - leukotrienes, tumor necrosis factor, interleukin-4 and other cytokines that turn on other inflammatory cells.

These materials cause fluid to leak from the capillaries and white cells including neutrophils, T cells and eosinophils to leave the circulation. The end result is a "local inflammatory response", a red, itchy welt.

Cellsalive.com

Components of BloodHemostasis- 3 mechanismsVascular spasm

Contraction of tunica media

Platelet plugPlatelet aggregation

CoagulationFormation of fibrin

clot

Components of Blood

Hemostasis (cont.)Fibrinolysis

Lysis of clot (plasmin)Thrombosis

ThrombolyticsMedications affecting clot formation

Alter the enzyme on the platelet.

Affect the coagulation cascade. Enhance clotting.

Coagulation Cascade - Synopsis

This scanning electron micrograph shows the fine structure of a blood clot. Platelets released from the circulation and exposed to the air use fibrinogen from the blood plasma to spin a mesh of fibrin.

General Assessment - Management

Focused History and Physical Exam SAMPLE history

Hematological disorders are rarely the chief complaint.

Physical exam Evaluate nervous

system function. Skin signs

General Assessment - ManagementPhysical Exam (cont.)

Lymphatic signs Gastrointestinal signs

Epistaxis Atraumatic bleeding gums Thrush Atraumatic splenic/hepatic pain

Musculoskeletal signs Arthralgia (rheumatoid arthritis) Hemarthrosis

Cardiorespiratory signs Tachycardia, cx pn, dyspnea - CHF

Genitourinary signs Hematuria Menorrhagia Infection

Blood Products and Blood Typing

Blood Typing - ABO

Blood type Antigen present on erythrocyte

Antibody present in

serum

OABBA

NoneA and B

BA

Anti-A, Anti-BNoneAnti-AAnti-B

Blood Products and Blood TypingCompatibility Among ABO Blood

Groups Reaction with serum of Recipient

Donor Cells AB B A O

ABBAO

----

+-+-

++--

+++--= no reaction

+ = reaction

Blood Products and Blood Typing

Brady; Paramedic Care Principles and Practice

Diseases of Erythrocytes

Anemias Anemia is a sign, not a separate disease process.

Signs and symptoms may not be present until the body is stressed.

Differentiate chronic anemia from acute episode.

Treat signs and symptoms. Maximize oxygenation and limit blood loss. Establish IV therapy if indicated.

Diseases of Erythrocytes

Brady; Paramedic Care Principles and Practice

Diseases of Erythrocytes

Sickle Cell Disease Normal red cells maintain

their shape as they pass through the capillaries and release oxygen to the peripheral tissues (upper panel). Hemoglobin polymers form in the sickle rell cells with oxygen release, causing them to deform. The deformed cells block the flow of cells and interrupt the delivery of oxygen to the tissues (lower panel).

Diseases of ErythrocytesSickle Cell Disease (cont.) Sickle cell crises

Vaso-occlusive Musculoskeletal/abdominal pain Priapism Renal/cerebral infarctions

Hematological Lowered hemoglobin Splenic sequestration

Infectious

Management Follow general treatment guidelines prn. Consider analgesics.

Diseases of Erythrocytes

PolycythemiaOverproduction of erythrocytes.

Occurs in patients > 50 years old or with secondary dehydration.

Most deaths due to thrombosisResults in bleeding abnormalities:

Epistaxis, spontaneous bruising, GI bleeding.Management:

Follow general treatment guidelines.

Diseases of Leukocytes

Leukopenia/NeutropeniaToo few white blood cells or neutrophils.Follow general treatment guidelines and

provide supportive care.

LeukocytosisAn increase in the number of circulating

white blood cells, often due to infection.Leukemoid reaction

Diseases of LeukocytesLeukemiaCancer of hematopoietic cells Initial presentation

Acutely ill, fatigued, febrile and weak, anemic.ThrombocytopeniaOften have a secondary infection.

ManagementFollow general treatment guidelines.Utilize isolation techniques to limit risk of infection.

Diseases of Leukocytes

Lymphomas Cancers of the lymphatic system

Hodgkin's Non-Hodgkins

Presentation Swelling of the lymph nodes Fever, night sweats, anorexia, weight loss, fatigue, and

pruritis Management

Follow general treatment guidelines. Utilize isolation techniques to limit risk of infection.

Clotting Disorders

Thrombocytosis and Thrombocytopenia Thrombocytosis

An abnormal increase in the number of platelets Thrombocytopenia

An abnormal decrease in the number of platelets Sequestration Destruction (ITP) Decreased production

Management Provide supportive care and follow general treatment

guidelines.

Clotting Disorders

Hemophilia Deficiency or absence of a blood clotting factor

Deficiency of factor VIII causes hemophilia A. Deficiency of factor IX causes hemophilia B. Deficiency is a sex-linked, inherited disorder.

Defective gene is carried on the X chromosome.

Signs & Symptoms Numerous bruises, deep muscle bleeding, and joint

bleeding.

Clotting Disorders

Hemophilia (cont.) Management

Treat the patient similarly to others. Administer supplemental oxygen. Establish IV access.

Be alert for recurrent or prolonged bleeding, and prevent additional trauma.

Von Willebrand’s Disease Deficient component of factor VIII

Generally results in excessive bleeding. Generally is not serious; provide supportive care.

Clotting Disorders

Disseminated Intravascular Coagulation

Components of Blood

Leukocytes (cont.)Autoimmune disease

May be specific or generalAlterations in the immune process

Immunosuppression HIV Anti-rejection medication Chemotherapy/Cancer

System activation of coagulation cascade.Results from sepsis, hypotension, OB complications, severe tissue or brain

injury, cancer, and major hemolytic reactions.

Multiple MyelomaCancerous disorder of plasma cells.Pathologic fractures are common.

Anticoagulants/Antiplatelets

Classifying agentsAnticoagulants

Block synthesis and activation of clotting factors

Antiplatelets Interfere with platelet aggregation or activation

FibrinolyticsDissolve fibrin component of thrombi

Anticoagulants/Antiplatelets

Anticoagulants Warfarin

Blocks activation of Vit K Interferes w/ coagulation factors II, VII, IX, and X

Unfractionated Heparin Binds antithrombin III (AT-III) Inhibits coagulation factors IX and X and thrombin

Hirudin (medicinal leech) Prevents thrombin binding

Anticoagulants/Antiplatelets

AntiplateletsAspirin

Prevents platelet activation through cyclooxygenase blockade.

Prevents production of thromboxane A2

Allows prostacyclin synthesis

TiclodipineDeforms platelet membrane fibrinogen receptor

Anticoagulants/AntiplateletsAntiplatelets (cont.) Glycoprotein IIb-IIIa Receptor Inhibitors

G IIb-IIIa = platelet membrane receptor of fibrinogen Abciximab Eptifibatide Tirofiban

Fibrinolytics Activate plasminogen to plasmin = fibrinolysis

Streptokinase Anistreplase Tissue Plasminogen Activator Reteplase Urokinase

HemorrhageClass I Class II Class III Class IV

Blood Loss (ml) Up to 750 750-1500 1500-2000 >2000

Blood Loss (% volume)

Up to 15%

15%-30% 30%-40% >40%

Pulse <100 >100 >120 >140

BP Normal Normal Decreased Decreased

Pulse Pressure Normal or increased

Decreased

Decreased Decreased

Resp. Rate 14-20 20-30 30-40 >35

Urine Output (ml/hr)

>30 20-30 5-15 Negligible

Mental Status Slightly anxious

Mildly anxious

Anxious, confused

Confused, lethargic

Fluid Replacement (3:1) rule

Crystalloid

Crystalloid

Crystalloid and blood

Crystalloid and blood

Transfusion Reactions

Hemolytic Reaction Signs & Symptoms

Facial flushing, hyperventilation, tachycardia, hives, chest pain, wheezing, fever, chills, and cyanosis

Treatment Stop transfusion, change all IV tubing, and initiate IV

therapy with normal saline or lactated Ringer’s. Consider furosemide, dopamine, and diphenhydramine.

Transfusion Reactions

Febrile Non-hemolytic ReactionsSigns & Symptoms

Headache, fever, and chillsTreatment

Stop transfusion, change all IV tubing, and initiate IV therapy with normal saline or lactated Ringer’s.

Consider Diphenhydramine and an antipyretic.Observe closely to ensure reaction is non-

hemolytic.