Hematology

what is hematology?

the study of blood and its diseases

what are the components of blood?

in 5 L of blood per 70 kg (154 lb) adult:

• 2.25 L (45%) are cells

• 1.6% leukocytes (WBCs)

• <1% thrombocytes (platelets)

• 55% plasma

what components make up plasma?

water (92%), gases (O2 and CO2), proteins (7%) (albumin, globulins, fibrinogen, complement system, clotting factors, ferritin, immunoglobulins), other small particles: steroid hormones, salts/electrolytes, lipids, CHO

what components make up cells within blood?

RBC (most numerous), WBCs, platelets

what are the 3 functions of blood?

transport, protection, regulation

what is transported within blood?

gases (O2, CO2), hormones, nutrients, waste products, heat

how does blood protect the human body?

immune system (WBCs, antibodies, cytokines), platelets and clotting factors

what does blood regulate?

pH and water

what is a Complete Blood Count?

a test used to measure the complete count of the components within blood

T/F: RBCs have a nucleus and cannot be transfused

false; WBCs are the ones with nuclei and cannot be transfused

hematopoiesis across the lifespan - embryo

yolk sac -> liver -> bone marrow by 5 mo gestation

hematopoiesis across the lifespan - fetus

bone marrow of all bones, liver and spleen

hematopoiesis across the lifespan - birth

bone marrow of all bones, not liver/spleen

what are the effects of aging on the hematopoietic system?

• incr fragility of plasma membranes, incr fibrinogen, incr platelet adhesiveness, incr RBC rigidity, early activation of coagulation system (more rigid as you age)

• changes cause disturbed blood; leads to development or aggravation of circulatory disorders

• decr #/size of lymph nodes, decr lymphocyte function, decr cellular immunity/t-cell function

hemoglobin

iron containing protein that allows RBCs to carry O2

• 4 globin chains + 4 heme units

myoglobin

stores O2 in mm

erythrocytes

(RBCs) most numerous; produced in BM, gradually filled with hemoglobin, mature RBC has no nucleus or organelles (120 day lifespan)

what is heme

porphyrin and iron

bright red blood signifies oxygenated or deoxygenated blood?

oxygenated

dark red blood signifies oxygenated or deoxygenated blood?

deoxygenated

how is SaO2 measured?

arterially

what is SpO2?

peripherally; noninvasive measurement of circulating oxygen

what is the oxygen-hemoglobin dissociation curve?

how readily Hbg acquires and released O2 into the fluid surrounding it

platelets (thrombocytes)

primary role is hemostasis; mature cells lack nucleus ( 7 day lifespan)

what is hemostasis?

arrest of bleeding from an injured blood vessel occurs within interaction of 3 processes

primary hemostasis:

steps 1&2 of hemostasis: vasoconstriction, platelet plug/activation

secondary hemostasis:

step 3 of hemostasis:

• fibrin clot forms via coagulation cascade -> fibrinogen (soluble plasma protein) -> fibrin (non-soluble plasma protein)

what are the vascular factors of hemostasis?

• local vasoconstriction, compression of injured vessel via blood in surrounding tissue

• vessel wall injury triggers attachment, activation of platelets -> fibrin

• platelets + fibrin = clot

what are the platelet factors of hemostasis?

disruption of vascular endothelial cell nitric oxide and prostacyclin production -> platelets aggregate and adhere to damaged intima -> platelet activation -> hydrolysis of cell membrane phospholipids -> arachidonic acid cascade -> thomboxane, other mediators -> fibrin

what are the coagulation factors of hemostasis?

• vessel damage releases tissue factor -> converts prothrombin to thrombin -> promotes fibrinogen to fibrin to form clot (coagulation cascade)

• mechanisms to prevent uncontrolled coagulation (inactivation of procoagulant enzymes, fibrinolysis)

inactivation of procoagulant enzymes

plasma protein inhibitors

fibrinolysis

plasminogen activations

hematocrit (Hct)

% of RBCs in blood

anemia

reduction in Hgb/Hct concentration of blood (due to abnormality in quantity or quality of RBCs) leading to decreased oxygen carrying capacity of RBCs

T/F: females have higher levels of Hct and Hgb

false; males do

what is the etiology of anemia?

decr RBC production, incr RBC destruction, excessive blood loss

iron deficiency anemia

anemia caused by inadequate iron intake; chronic GI blood loss, heavy menstruation

anemia of inflammatory/chronic disease

RA, SLE, chronic inflammation -> incr ferritin in macrophages -> iron cannot be transferred or recycled to bone marrow to make new RBCs

nutritional deficiency anemia

folate, vitamin B12, iron

infectious diseases (anemia of chronic disease)

TB, AIDs

neoplastic disease

bone marrow failure, radiation, chemo

T/F: individuals with anemia have sufficient oxygen in their blood

false; they have inadequate blood

what are SXS of anemia?

weakness, dyspnea on exertion, fatigue, pallor of skin/mucosa, tachycardia, angina

how do you treat anemia?

blood transfusion; need to find the underlying cause of anemia and to hemodynamic instability

is 8g/dL an appropriate threshold for someone with anemia to exercise?

anything below 8 = no exercise

how would you provide treatment to patients with anemia?

you need to adjust exercise and other mobility interventions based on their Hgb levels and be on the lookout for s/s (weakness, fatigue, dizziness, SOB)

normocytic

acute hemorrhage

microcytic

iron deficiency, MCV

macrocytic

vitamin b12, folate deficiency

hypochromic

iron deficiency, MCH

poikilocytosis

various shapes-spherocytes, sickle cells

hemolytic

destruction of red blood cells

what is sickle cell disease?

• most common inherited hematologic disorder worldwide

• autosomal recessive inheritance: need to inherit one abnormal HgbS from each parent -> HgbSS

• unstable RBCs can be triggered

what change do RBCs go through due to sickle cell disease?

biconcave discs to sickle shape

one parent with disease, one with trait =

50% chance per pregnancy of having a child with HbSS

one parent with disease, one without disease or trait =

100% chance per pregnancy of having child with trait (carrier)

both parents with trait =

25% chance per pregnancy of having child with HbSS

50% of individuals with sickle cell disease live in...

nigeria, india, DRC

what does the sickle cell trait give individuals?

protection from malaria

sickle cell causes RBCs to...

lose ability to deform and squeeze through small vessels

what is the average lifespan of a sickle cell?

10-20 days

what are the 2 primary pathophysiologic features of sickle cell disease?

vaso-occlusion (cause ischemic injury), chronic hemolytic anemia

what is aplastic?

certain viral infections can cause abrupt and severe bone marrow fx

what is a predominant symptom of sickle cell disease?

pain

what are complications of SCD?

altered splenic function, hand-foot syndrome, chronic leg ulcers, neurologic, acute chest syndrome (pneumonia), joint pain (typically episodic)

what are treatments for sickle cell disease?

prevent crisis, drugs to prevent sickling, address anemia, supportive care for pain/occlusive crises, disease modifiers in order to decr sickling

what can PTs do to treat SCD?

• exercise: avoid stressors

• acute chest crisis: improve ventilation and oxygenation

• promote non-opioid pain relief: opioid use is higher among people with SCD

autologous blood transfusions

banked individuals own blood

recombinant human erythropoietin

the laboratory production of human erythropoietin; stimulates productions of own blood cells

what components can be transfused in blood?

RBCs, platelets, fresh frozen plasma (FFP) and recombinant plasma factors

what is leukoreduction?

filtration of WBCs from RBC products

what are complications of transfusions?

febrile, non-hemolytic reaction, acute hemolytic transfusion reaction, transfusion related acute lung injury, delayed hemolytic transfusion reaction, allergic reaction, anaphylaxis, septic reaction, circulatory overload, iron overload, air embolism, disease transmission

what is polycythemia?

incr in the number of RBCs in the body

primary polycythemia

• aka polycythemia vera; incr RBC production in bone without secondary cause (genetic)

• s/s: itching, joint pains, blood clots

• RX: blood letting, hydroxyurea, depends on severity

secondary polycythemia

• caused by incr erythropoietin excretion triggered by other conditions (chronic hypoxia, paraneoplastic syndrome)

• s/s: not recognizable

• RX: address underlying cause (COPD most common)

hemochromatosis

excessive iron absorption by small intestine (happens over time)

• autosomal recessive

T/F: individuals with hemochromatosis can have a normal life expectancy IF they have normal iron levels and no organ damage

true

what is a way to treat advanced hemochromatosis?

liver transplant

what do PTs need to consider with patients with hemochromatosis?

• arthritic changes

• differential diagnosis -> need to refer

• adjustments if liver dysfunction or secondary diabetes mellitus develops

how long can aspirin suppress platelet aggregation for?

~ 7 days

when platelets are inactivated, they can no longer...

synthesize enzymes and are inactive for life span

how long do NSAIDs suppress platelets for?

<24 hours

what is the coagulation cascade?

vessel damage -> tissue factor -> prothrombin to thrombin -> promotes fibrinogen to fibrin to form clot

where are coagulation factors produced?

liver

what is thrombophilia?

incr risk of thrombosis = clots forming in blood vessels

what is congenital thrombophilia?

• factor V, prothrombin (factor II) mutation

• produce overactivity of coagulation factors due to gene mutations

• deficiency of natural anticoagulants

what is acquired thrombophilia?

• myeloproliferative disorders

• obesity, pregnancy, estrogen, cancer, incr sitting

what is Virchow's Triad?

stasis, endothelial injury, hypercoagulability (combination of factors that elevate risk of VTE)

hemostasis requires:

• normal # and function of platelets (primary hemostasis)

• normal clotting factors (secondary hemostasis)

what is von Willebrand Disease?

most common inherited disorder of hemostasis due to lack or dysfunction of von Willebrand Factor

etiology of thrombocytopenia

decr platelet production in bone marrow, incr platelet destruction (too few)

etiology of thrombocytosis

abnormal, accelerated platelet production in bone marrow

what is disseminated intravascular coagulation?

overactivation of the coagulation cascade

• RX: reverse underlying condition

what is hemophilia?

x-linked recessive trait, most common inherited coagulation disorder

• excessive bleeding!

hemophilia A

factor VIII deficiency

hemophilia B

factor IX deficiency

what activates factor 10?

both factor 8 and 9

where are factor VIII and factor IX made?

the liver

iyonization

female carriers may have very low levels of fxVIII or fxIX, which occurs when one of the 2 X-chromosomes are randomly inactivated

how can PTs help with hemophilia?

protective strengthening of mm around affected joints, gait training, maintain positioning and prevention of further deformity, patient education