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HEMATOLOGIC SYSTEM. Ch. 14 Goodman. OVERVIEW. *The hematologic system involves the blood, blood vessels and the associated organs. *The study of hematology includes the diseases of the hematological system.

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hematologic system

HEMATOLOGIC SYSTEM

Ch. 14

Goodman

overview
OVERVIEW
  • *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
components of blood
COMPONENTS OF BLOOD
  • *2 components of blood:
    • Plasma
    • Formed elements
      • Erythrocytes (RBCs)
      • Leukocytes (WBCs)
      • Thrombocytes (platelets)
signs of hematological disorders
SIGNS OF HEMATOLOGICALDISORDERS
  • 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

more signs
MORE SIGNS….
  • Lymphedema (sign)

Can be a sign of hematologic conditions - increased lymphatic load associated with

decreased 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

and still more
AND STILL MORE…
  • Lymphedenopathy (sign)

Abnormal enlargement of lymph nodes

  • Splenomegaly

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

aging hematopoietic system
AGING/HEMATOPOIETIC SYSTEM
  • 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
blood transfusion reactions
BLOOD TRANSFUSION REACTIONS
  • 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 distress

syndrome (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 to

ABO incompatibility; RBCs are destroyed (lysis) - mortality rate is high (17-60%)

blood transfusion reactions continued
BLOOD TRANSFUSION REACTIONS (CONTINUED):
  • 4. Allergic reactions - 1-3% of all transfusions, most common with fresh frozen plasma

and 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
disorders of iron absorption
DISORDERS of IRON ABSORPTION
  • Disorders of Iron Absorption
  • Hereditary Hemochromatosisis an autosomal recessive hereditary disorder characterized

by excessive iron absorption by small intestine

  • Uncoupling of absorption and needs - leads to iron deposition in cells, particularly the

liver, pancreas and heart

  • Early signs include weakness, hepatomegaly, elevated liver enzymes; symptoms include

myalgias, joint pain, fatigue

hereditary hemochromatosis continued
Hereditary Hemochromatosis (continued)
  • Diagnosis-by blood work
  • Treatment - therapeutic phlebotomy
  • Prognosis -is good (from a mortality / morbidity perspective) but the condition is not reversible - it is managed
disorders of erythrocytes
DISORDERS OF ERYTHROCYTES
  • 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
a nemia continued
Anemia (continued)
  • 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 destruction

and production of RBCs

anemia continued
Anemia (continued)
  • 3. Clinical manifestations
  • Mild - minimal and vague symptoms of fatigue
  • Moderate to severe progression: weakness, dyspnea on exertion, tachycardia, increased

angina in pre existing CAD, dementia

  • 4. Treatment
  • a. Underlying problem (cause) if possible
  • b. Blood transfusions
d isorders of leukocytes
DISORDERS OF LEUKOCYTES
  • 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

** Treatment

Underlying problem

d isorders of leukocytes1
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

neoplastic diseases of the blood and lymph systems
NEOPLASTIC DISEASES OF THE BLOOD AND LYMPH SYSTEMS
  • **** Bone marrow transplant

Treatment 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
l eukemia continued
Leukemia (continued)
  • 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
malignant lymphomas
MALIGNANT LYMPHOMAS
  • 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

hodgkin s lymphoma
Hodgkin’s Lymphoma
  • 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)

non hodgkin s lymphoma
Non-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

multiple myeloma
MULTIPLE MYELOMA
  • Multiple Myeloma
  • MM - primary malignant neoplasm of plasma cells arising in bone marrow
  • Progression causes damage to kidney, recurrent infections, often affects the nervous

system

  • Increased incidence (doubled in past 2 decades) (~16,000 new cases / year) - thought in part to increase in population > 85 years old
myeloproliferative disorders
MYELOPROLIFERATIVE DISORDERS
  • Myeloproliferative Disorders
  • Originate from a hematopoietic stem cell that has transformed to allow the cell to mature

and 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
types of myeloproliferative disorders
Types of Myeloproliferative Disorders
  • Polycythemiavera - increased production of RBCs
  • Essential thrombocythemia - most common - increased platelet count
disorders of hemostasis
DISORDERS OF HEMOSTASIS
  • Disorders of Hemostasis
  • Primary hemostasis - formation of a platelet plug (collagen fibrils and von Willebrand’s

factor (vWF) in the subendothelial matrix of the blood vessel gets exposed to blood)

  • Secondary hemostasis - vascular damage exposes tissue damage
disorders of h emostasis
Disorders of hemostasis
  • A. von Willebrandʼs Disease
  • Most common inherited bleeding disorder -
  • Disorder of primary hemostasis - mucosal and skin bleeding and prolonged oozing after

trauma or surgery

  • Rx - replacement of vWF
disorders of hemostasis1
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 hemostasis2
Disorders of hemostasis
  • C. Thrombocytopenia
  • Decreased platelets (< 150,000/mm^3) - caused by either reduced production or

increased 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 hemostasis3
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 hemostasis4
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 vascular

system

  • 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 hemostasis5
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) shape

once oxygen is released - provides selective immunity to malaria but leads to

difficulty in blood flow in microvascular resulting in acute and chronic tissue injury

disorders of hemostasis6
Disorders of hemostasis
  • Acute crises or episodes - pain caused by blockages of sickled RBCs in any

organ, 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 hemostasis7
Disorders of hemostasis
  • 2. Thalassemias- inherited disorder with abnormalities in one of more of the 4 globin

genes; 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
slide34

Created by:

Andrea C. Mendes PT, DPT

and

Sean M. Collins PT, ScD