HEMATOLOGIC SYSTEM

Ch. 14Goodman

*The hematologic system involves the blood, blood vessels and the associated organs.

*The study of hematology includes the diseases of the hematological system.

* This critical system is tightly integrated with the following systems: lymphatic, immune, circulatory, respiratory. It is also integrated with hormonal and metabolic functions.

***While there are primary diseases of the hematological system, the most common conditions are most often signs of other conditions

OVERVIEW

*2 components of blood:◦ Plasma◦ Formed elements

Erythrocytes (RBCs) Leukocytes (WBCs) Thrombocytes (platelets)

COMPONENTS OF BLOOD

Edema (sign)Excessive fluid accumulation within the interstitial tissues or within body cavities

Infarction (sign)localized region of necrosis caused by reduction of arterial perfusion

Thrombus (sign)blood clot - solid mass within intact vessel or the heart

Embolus (sign)Thrombus on the move that gets lodged distant from its place of origin

SIGNS OF HEMATOLOGICALDISORDERS

Lymphedema (sign)Can be a sign of hematologic conditions - increased lymphatic load associated withdecreased plasma proteins

Bleeding / bruising (sign)A sign when it happens with minor trauma or if bleeding continues longer than normal

Shock (sign)Inadequate blood pressure to perfuse organs

MORE SIGNS….

Lymphedenopathy (sign)Abnormal enlargement of lymph nodes

Splenomegalyenlarged spleen (spleen removes old RBC’s and antibody-laden bacteria or cells)

AND STILL MORE…

Aging and the Hematopoietic System Decreased red marrow Decreased intestinal iron absorption Increased fragility of plasma membranes Increased fibrinogen and platelet

adhesiveness Earlier activation of coagulation system (ergo…) disturbed blood flow, propensity

for anemia (low RBCs) - if nothing else slower RBC recovery from a loss of blood

AGING/HEMATOPOIETIC SYSTEM

Blood Transfusions Reaction to blood and blood products 1. Febrile nonhemolytic reaction - most common (.5-1% of

transfusions), fever (at least 1 degree rise) but stable cells 2. Transfusion related acute lung injury - 1 in every 2000

transfusions; initially mild shortness of breath but can progress to appear clinically as acute respiratory distresssyndrome (widespread inflammation, low ventilatory volumes, poor oxygenation); with treatment can prevent / minimize permanent lung damage

3. Acute hemolytic transfusion - 1 in every 25,000 transfusions - severe response due toABO incompatibility; RBCs are destroyed (lysis) - mortality rate is high (17-60%)

BLOOD TRANSFUSION REACTIONS

4. Allergic reactions - 1-3% of all transfusions, most common with fresh frozen plasmaand platelet transfusions - allergic reaction

5. Anaphylaxis - 1 in 20,000 transfusions - acute onset of hypotension, laryngeal edema

6. Sepsis - very rare; due to bacterial contamination of blood products used in transfusion

Bloodless medicine - goal to reduce blood loss with procedures to avoid need of transfusions

BLOOD TRANSFUSION REACTIONS (CONTINUED):

Disorders of Iron Absorption Hereditary Hemochromatosis is an autosomal

recessive hereditary disorder characterizedby excessive iron absorption by small intestine

Uncoupling of absorption and needs - leads to iron deposition in cells, particularly theliver, pancreas and heart

Early signs include weakness, hepatomegaly, elevated liver enzymes; symptoms includemyalgias, joint pain, fatigue

DISORDERS of IRON ABSORPTION

Diagnosis -by blood work Treatment - therapeutic phlebotomy Prognosis -is good (from a mortality /

morbidity perspective) but the condition is not reversible - it is managed

Hereditary Hemochromatosis (continued)

Anemia 1. Definition reduction in oxygen carrying capacity of

blood due to reduced quantity or quality of RBCs HgB < 14 g/100 ml for men; 12 g/ 100 ml

for women

DISORDERS OF ERYTHROCYTES

2. Overview Not technically a disease - really a sign of other

underlying disorders - including but not limited to: ** dietary (folate, vitamin B12) **acute or chronic blood loss ** iron deficiency (diet or absorption) ** congenital defects (sickle cell anemia) **poison exposure ** disease of bone marrow **chronic inflammatory, infectious or neoplastic disease ** any disorder that upsets the balance between blood

loss through bleeding or destructionand production of RBCs

Anemia (continued)

3. Clinical manifestations Mild - minimal and vague symptoms of

fatigue Moderate to severe progression: weakness,

dyspnea on exertion, tachycardia, increasedangina in pre existing CAD, dementia

4. Treatment a. Underlying problem (cause) if possible b. Blood transfusions

Anemia (continued)

Disorders of Leukocytes A. Leukocytosis

** Definition & Etiology Increased number of leukocytes (WBCs) for a variety

of causes - including as a normal response stressors Common finding with infection - > 10,000

WBCs/mm^3**Clinical manifestations

Signs and symptoms are usually those of infectious conditions (localized or systemic) -fever, headache, shortness of breath

** TreatmentUnderlying problem

DISORDERS OF LEUKOCYTES

B. Leukopenia**Definition & Etiology

Decreased number of WBCs - < 5000 / ml caused by a variety of conditions:* HIV, hepatitis*alcohol* Nutritional deficiencies*connective tissue disorders (SLE)* bone marrow failure (i.e. following antineoplastic chemotherapy)**Clinical manifestations

Asymptomatic; increased risk of infection**Treatment

Underlying problem

Disorders of Leukocytes

**** Bone marrow transplantTreatment of choice for any hematologic neoplastic disease A. Leukemias Malignant neoplasm of blood forming cells that replaces normal bone

marrow with a malignant clone Acute vs. Chronic Myeloid vs. Lymphocytic Blastic vs. cytic Acute progresses quickly; chronic slowly Myeloid - bone marrow origin involving hematopoeitic stem cells Lympho - involving lymphoid or lymphatic system Blastic - large, immature (functionless) cells cytic - immature, smaller cells Immunologically can also classify as T-cell / natural killer cell and B-cell

leukemias

NEOPLASTIC DISEASES OF THE BLOOD AND LYMPH SYSTEMS

Three main clinical consequences: 1. Anemia 2. Infection 3. Bleeding tendencies Acute myelogenous leukemia - AML - most common

leukemia in adults Acute lymphoblastic leukemia - ALL – diagnosed most

commonly in children Chronic myeloid leukemia - CML – occurs most often

in adults Chronic lymphocytic leukemia - CLL – a common type

of adult leukemia

Leukemia (continued)

Malignant Lymphomas Cancers of lymphatic system Two groups - Hodgkin’s lymphoma and Non-

Hodgkin’s Lymphoma (HL and NHL) - although the distinction has become less clear More useful to categorize based on cell behavior

- indolent vs. aggressive HL is distinguished from others by presence of a

cell known as the Reed-Sternberg cell in the lymph nodes

MALIGNANT LYMPHOMAS

HL - adults and children; B-cell malignancy; Clinical manifestations are variable, Box

14-6, Ann Arbor Staging Classification for HD (Hodgkin’s Disease) - progresses by increased involvement of lymph nodes and other lymph organs; Stage IV includes involvement of extralymphatic

organs (liver, lung, skin)

Hodgkin’s Lymphoma

NHL - large group (~30 types) of lymphoid malignancies that present as solid tumors

arising from lymphatic cells - 5th most common type of cancer in the US with an incidence of ~67,000 / year; clinical manifestations are variable

Non-Hodgkin’s Lymphoma

Multiple Myeloma MM - primary malignant neoplasm of plasma

cells arising in bone marrow Progression causes damage to kidney,

recurrent infections, often affects the nervoussystem

Increased incidence (doubled in past 2 decades) (~16,000 new cases / year) - thought in part to increase in population > 85 years old

MULTIPLE MYELOMA

Myeloproliferative Disorders Originate from a hematopoietic stem cell

that has transformed to allow the cell to matureand function with uncontrolled function - common characteristics include:

1. hypercellular bone marrow 2. tendency to thrombosis and hemorrhage 3. increased risk of evolving into acute

leukemia

MYELOPROLIFERATIVE DISORDERS

Polycythemia vera - increased production of RBCs

Essential thrombocythemia - most common - increased platelet count

Types of Myeloproliferative Disorders

Disorders of Hemostasis Primary hemostasis - formation of a platelet

plug (collagen fibrils and von Willebrand’sfactor (vWF) in the subendothelial matrix of the blood vessel gets exposed to blood)

Secondary hemostasis - vascular damage exposes tissue damage

DISORDERS OF HEMOSTASIS

A. von Willebrandʼs Disease Most common inherited bleeding disorder - Disorder of primary hemostasis - mucosal

and skin bleeding and prolonged oozing aftertrauma or surgery

Rx - replacement of vWF

Disorders of hemostasis

B. Hemophilia Deficiency of clotting factors Disorder of secondary hemostasis - easy

bruising, prolonged bleeding If severe can spontaneously bleed - into

joints, muscles, organs Rx - replacement of clotting factors

Disorders of hemostasis

C. Thrombocytopenia Decreased platelets (< 150,000/mm^3) -

caused by either reduced production orincreased destruction; usually a sign of other problems

Mucosal bleeding is a common sign May be presenting sign of aplastic anemia

(bone marrow failure) Rx - underlying cause; platelet transfusions

Disorders of hemostasis

D. Aspirin / NSAIDs Single dose of ASA can impair platelet

function for 48 hours NSAIDs are less potent ASA and NSAIDs are contraindicated before

surgery

Disorders of hemostasis

E. Disseminated Intravascular Coagulation DIC - thrombotic disease caused by overactivation of

the coagulation cascade - Paradoxical in that clotting and hemorrhage occur

simultaneously within the vascularsystem

Widespread clotting and fibrin deposition in circulation, causes backflow and increased pressure which leads to hemorrhage

Common after shock, sepsis, obsteteric / gynecological complications, cancer, massive trauma

Alteration in normal balance of pro and anticoagulant factors

Rx - underlying cause

Disorders of hemostasis

F. Hemoglobinopathies Abnormalities in the formation of HgB 1. Sickle cell disease (SCD) - Genetic, result is HgB that changes from

biconcave to crescent (sickle) shapeonce oxygen is released - provides selective immunity to malaria but leads todifficulty in blood flow in microvascular resulting in acute and chronic tissue injury

Disorders of hemostasis

Acute crises or episodes - pain caused by blockages of sickled RBCs in anyorgan, bone or joint; location and severity vary widely

Life threatening crises occur when these occur in chest (heart or lung) or CNS

Bone marrow transplant cures SCD Sickle Cell trait - makes both types of HgB -

rarely symptomatic

Disorders of hemostasis

2. Thalassemias - inherited disorder with abnormalities in one of more of the 4 globingenes; leads to varying degrees of abnormally functioning HgB

Clinical manifestations based on extent to which the globin genes are impacted and are related to:

1. defective synthesis of HgB 2. structurally impaired RBCs 3. hemolysis or destruction of RBCs (anemia)

\ impaired oxygen carrying capacity - Rx - transfusions

Disorders of hemostasis

and Sean M. Collins PT, ScD

Created by:Andrea C. Mendes PT, DPT