Blood Cells Immunity Blood Coags - Exam 2 Flashcards
Reb blood cells aka __ carry __, bearing __ to the tissues
erythrocytes; hemoglobin; O2
RBC’s contains ___, which catalyze what reaction
carbonic anhydrase
CO₂ + H₂O ➡ H₂CO₃
biconcave disc of RBC’s allow them to
travel through blood capillaries with ease
mature RBC’s lack
nucleus & mitochondria, thus they lack the power for cell division and rely on glucose for generating ATP
eyrothropoesis
formation of RBC’s
RBC count in men
5,200,000 mm³ +/- 300,000
RBC count in women
4,700,000 mm³ +/- 300,000
RBC counts can be increased at __ altitudes
higher
MCV
MCH
MCHC
mean cell volume
mean cell hgb
mean cell hgb conc
normal hgb concentration __ g per __ mL of packed cells
34 g per 100 mL
normal hematocrit
40-45%
“packed cell volume”
normal hgb
14-15g per 100 mL of blood
O₂ carrying capacity is
1.34 mL/g Hgb, or 19-20 mL O₂/100 mL of blood
hemoglobin structural unit:
- The predominant form in adults is Hgb A, with 2 ⍺ and 2 β chains
- each globin chain is associated with one heme group containing one atom of iron
- each of the four iron atoms can bind loosely with one molecule (2 atoms) of oxygen
- thus each Hgb molecule can transport 8 oxygen atoms
bone marrow has what specific cell
PHSC (pluripotent hematopoietic stem cell)
red bone marrow produces
2.5 million RBCs per sec
regulation of erythropoiesis
- process stimulated by erythropoietin (EPO)
- from the kidneys that respond to low blood O₂ levels
- process takes about 3 days
erythrocytes can be broken down into
heme and globin
- iron and heme can be recycled back to the body or it can be eliminated
- bilirubin forms from the breakdown of erythrocytes and travels to the liver and is then converted to bile can be absorbed by the small intestine and then can be eliminated as feces
- bile from the liver can also be recycled back to the kidneys and excreted as urine
if there is too much erythrocyte break down
spleen can become enlarged
factors that decrease oxygenation
- low blood volume
- anemia
- low Hgb
- poor blood flow
- pulmonary disease
this tells kidney to make erythropoietin, negative feeb-back loop
EPO
- circulating hormone
- necessary for erythropoiesis in response to hypoxia
- 〜90% made in the kidney
- cells of origin not established
response to hypoxia
- minutes to hours ↑ erythropoietin
- new circulating reticulocytes 〜 3 days
- EPO → drives production of proerythroblasts from HSCs, accelerates their maturation into RBCs
- can increase RBC production up to 10-fold
- EPO remains high until normal tissue oxygenation is restored
anemia
- reduced hgb in blood
- acute or chronic
- after hemorrhage: fluid volume restored in 1-3 days, RBC concentration restored in 3-6 weeks
Vitamin B12 & folic acid
- rapid, large-scale cellular proliferation requires optimal nutrition
- cell proliferation requires DNA replication
- both are needed to make thymidine triphosphate (thus, DNA)
- abnormal DNA replication causes failure of nuclear maturation and cell division → large irregular fragile “macrocytes”
pernicious anemia
- failure to absorb vitamin B12
- atrophic gastric mucosa: failure to produce intrinsic factor (intrinsic factor typically binds to vitamin B12) → protects it from digestion, binds to receptors in the ileum, mediates transport by pinocytosis
- vitamin B12 - stored in the liver, released as needed, thus normal stored are adequate for 3 - 4 years
folic acid present in
green vegetables, some fruits, and meats
folic acid deficiency
- destroyed during cooking
- subject to dietary deficiencies
- may also be deficient in cases of intestinal malabsorption
- maturation failure may reflect combined vitamin B12 and folate deficiency
circulatory effects of anemia
- decreased viscosity
- decreased O₂ (carrying capacity) → increases CO
- markedly decreased exercise capacity
polycythemia
- secondary to RBC count ↑
- chronic hypoxemia (heart or lung dx)
- physiologic polycythemia: living at 14 to 17 thousand feet higher, markedly enhanced exercise capacity at altitude
polycythemia vera
- clonal abnormality causing excessive proliferation
- usually all lineages
- 7 - 8 million RBCs, Hct 60-70%
- hyperviscosity up to 3-fold from normal
polycythemia & circulation
- increased viscosity decreases venous return
- increased blood volume increases venous return
- 2/3 normotensive, 1/3 hypertensive
- the subpapillary venous plexus under the skin becomes engorged with slow-moving, de-saturated blood, producing a ruddy complexion with a bluish tint to the skin
compensatory polycythemia
- sustained hypoxia can result in red cell mass above the usual normal range
- some of the causes include: prolonged stay at high altitude, lung dx, HF
first line of defense
mechanical barriers (skin & mucous membranes)
pathogen enters the body
Second line of defense:
- chemical barriers (enzymes, pH, salt, interferons, defenses, collectins, complement)
- natural killer cells
- inflammation
- phagocytosis
- fever
Third line of defense:
- cellular immune response
- humoral immune response
1st and 2nd line of defense combined is also known as
non-specific immunity or inet
type of WBCs
- polymorphonuclear neutrophils
- eosinophils
- basophils
- monocytes
- lymphocytes
circulate in the blood and may enter the tissues
WBC count
〜 7,000/ mm³ (almost a 1,000 fold fewer than RBCs)
proportions
- neutrophils 62% (1st)
- eosinophils 2.3%
- basophils 0.4%
- monocytes 5.3%
- lymphocytes 30% (2nd)
myeloid stem cell lineage
- RBC
- Granular leukocytes: eosinophil, basophil, neutrophil
- monocyte
- platelets
lymphoid stell cell lineage
- B-cell
- T-cell
neutrophils are __ cells that can respond __ to infection
mature; immedatley
monocytes mature in the __ to become __
tissues; macrophages
both exhibit motility:
- diapedesis
- ameboid motion
- chemotaxis (chemoattractants: bacterla or tissue degradation products, complement fragments, other chemical mediators)
phagocytosis
ingestion of particles
- must distinguish foreign particles from host tissues
*toll-like receptors (TLRs): sensors for innate immune response. Fc receptors are detectors for adaptive immune response *
specialized macrophages
- skin, subcutaneous (histiocytes)
- lymph nodes: ingest/sample particles arriving through lymph
- alveolar macrophages: digest or entrap inhaled particles and microorganisms
- kupffer cells: surveillance or the portal circulation
- macrophages in the spleen and bone marrow: surveillance of the general circulation
inflammation is driven by __ mediators and caharacterized by:
chemical
heat, redness, swelling and pain
physiologically, it involves:
- vasodilation and increased blood flow
- increased capillary permeability
- coagulation of interstitial fluids
- accumulation of granulocytes and monocytes
- swelling of tissue cells
inflammatory mediators
histamine, bradykinin, serotonin, prostaglandins, complement products, clotting components, cytokines, lymphokines
different type of cytokines
interleukin 1, TNF- alpha, interleukin 6, interleukin 2, intereferons (type I & II), chemokines, colony-stimulating factors
neutrophilia
increase in neutrophil count
- with intense inflammation, neutrophil can increase dramatically
- results from mobilization of mature neutrophils form the bone marrow by inflammatory mediators
formation of pus:
- is composed of dead bacteria and neutrophils, many dead macrophages, necrotic tissue that has been degraded by proteases, and tissue fluid, often in a cavity formed at the inflammatory site
- over days or weeks it is absorbed into the surrounding tissue and lymph and disappears
eosinophils
- are weak phagocytes and exhibit chemotaxis
- particularly important in defense against parasites
- can adhere to parasites and release substances that kill them (hydrolases, reactive oxygen species, major basic protein)
- also accumulate in tissues affected by allergies, perhaps in response to eosinophil chemotactic factor from basophils (eosinophils may detoxify some products of basophils)
basophils
- similar to mast cell adjacent in capillaries… both cell types release heparin
- basophils and mast cells both release histamine, bradykinin, and serotonin
- when IgE bound to receptors on their surface is cross-linked by its specific antigen, mast cells and basophils degranulate, releasing: histamine, bradykinin, serotonin, heparin, leukotrienes, and several lysosomal enzymes
leukopenia
- low WBC count, usually the result of reduced production of cells by the bone marrow
- it can allow clinically severe infections with organisms that are not usually pathogenic
within __ days of bonemarrow shut down, mucous membrane __ or resp __ may occur
2; ulcer; infection
causes of leukopenia
radiation, chemical toxins, some medicines
in most cases marrow precursors can reconstitute normal blood cell counts with proper support
leukemia
- uncontrolled production of abnormal WBCs d/t a genetic mutation
- clonal, lineage-specific, often immature cells
leukemias are:
- lymphocytic vs. myelogenous
- acute vs. chronic (sometimes up to 10-20 yrs)
leukemias with partially differentiated cells may be classified as
neutrophilic, eosinophilic, basophilic, monocytic leukemias
clinical effects of leukemias
- growth of leukemic cells in abnormal sites
- invasion of bone from the marrow, with pathologic fractures
- eventually spreads to vascular and lymphatic “filters” such as the spleen, lymph nodes, liver, and other organs
- replacement of normal bone marrow, resulting in infection, and bleeding
- wasting b/c of metabolic demands
innate immunity
- non-specific
- 1st and 2nd line
- inborn ability to resist damaging organisms and toxins: skin, gastric acids, tissue neutrophils, and macrophages, complement microbicidal and lytic chemicals in blood and blood cells
acquired / adaptive (specific) immunity
humoral → circulating antibodies
cellular → activated cells
antibodies are __ cells that specifically target and destroy invading __ & toxins
activated; organisms
very powerful: can neutralize 100,000 x the lethal dose of some toxins
antigen
- a substance that can elicit an immune response
- unique to each invading organism
- usually proteins or large polysaccharides
- most are large and have recurring molecular groups on their surface
- the molecular structures that are specifically recognized in acquired immunity are called “epitopes”
2 types of lymphocytes
T-cells and B-cells
lymphocytes mediate __ immunity
acquired
where do lymphocytes develop?
lymphoid tissues: tonsils, adenoids, peyer’s patches(GI), lymph nodes, speen, thymus, marrow
maturation of T cells in the thymus
- rapid expansion
- each clone is specific for a single antigen
- self-reactive clones are deleted (up to 90%)
- migrate to peripheral lymphoid organs
much of the above occurs just before and slightly after birth
B cell development and proliferation in response to antigen
- initial growth and differentiation in the liver (fetal) and bone marrow (after birth)
- migrate to the peripheral lymphoid organs
- each clone is specific for a single antigen
- clonal development provides an almost limitless antibody specificity
- secreted antibodies destroy and neutralize molecules or organisms hearing their cognate antigen
each B or T cell clone is specific for a single __ of a single __
epitope; antigen
- the genes for B & T cell receptors have hundreds of “cassettes” that are used in varying combinations
- permutations of these cassettes allow specificity for millions of distinct epitopes
lymphocyte activation
- macrophages in lymphoid organs → ingest antigen and present antigenic peptides to “helper” T cells
- secrete IL-1, other cytokines that promote lymphocyte growth and differentiation
- Helper T cells produce additional cytokines that stimulate B and T cell proliferation and differentiation
- both B & T cells require antigenic stimulation to proliferate
B-cell activation and antibody production
- B cells bind to intact antigen
- B cells proliferate (with T cell help), developing lymphoblasts and plasmablasts
- can persist for many weeks, if antigenic stimulation persists
Antibody/immunoglobulin: structure & sepcificity
- at least bivalent (2 antigen-binding sites)
- each antibody has a steric configuration specific to its antigen
- multiple prosthetic groups of each antigen interact with complementary structures of the antibody through: hydrophobic bonding, hydrogen bonding, ionic interactions, van der Waals forces
antibody classes
IgM, IgG, IgA(breast milk), IgD(less than 1%), IgE
immunoglobulins make up about 20% of all plasma proteins
What’s the earliest produced antibody?
IgM
whats the most abundant antibody?
IgG (75% of all immunoglobulins)
cross the placenta
which immunoglobulin is involved in allergic reactions?
IgE
antibodies: mechanisms of action
- precipitation: makes soluble antigens insoluble, aiding elimination
- agglutination: links cell-bound antigens together, causing clumping
- neutralization: masks dangerous parts of the pathogen (exp. exotoxins)
- inflammation: triggers histamine release, increasing immune motility
the 4 above all enhance opsonization & phagocytosis
- complement: complement protein perforated the cell membrane (cell lysis)
T cell activation (involvement of MHC proteins and antigen presentation)
- T cells only recognize antigen fragments that are presented by MHC molecules of antigen-presenting cells(APCs): macrophages, B lymphocytes, dendritic cells
MHC molecules
- encoded by the major histocompatibility complex
- MHC I - present to cytotoxic T cells (CD8) **
- MHC II - present to helper t cells (CD4) **
- antigen in the context of MHC is recognized by as many as 100,000 T cell receptors per cell
Helper T cells (CD4)
- 〜75% of all T cells
- regulate functions of other immunologic cells by producing cytokines: IL-2,3,4,5,6, GM-CSF, interferon-gamma
- positive feedback for helper T cells
- stimulation of cytotoxic T cells
- stimulation of B cells
- macrophage accumulation, activation, enhanced killing
General steps for helper T cell activation:
- binds to cognate antigen presented by APC
- rapid expansion of T helper (CD4) cells
- T helper cells produce cytokines
- drives expansion of both T helper (CD4) and cytotoxic (CD8) T cells
- both types of cells also generate clonal memory T cells
Immunologic tolerance
- host defense employs powerful destructive mechanisms
- these must be directed at pathogens while protecting host tissues from damage **
- “Tolerance” in acquired immunity is achieved mainly by clonal selection of T cells in the thymus and B cells in the bone marrow → clones that bind host antigens with high affinity are induced to undergo apoptosis, and are deleted
Cytotoxic T (CD8) cells
- virus-infected cells
- cancer cells
- transplanted organs and tissues
failure of immunologic tolerance results in
autoimmunity
- rheumatic fever: cross-reactivity with streptococcal antigens
- post-streptococcal glomerulonephritis
- myasthenia gravis: antibodies to ACh receptors
- systemic lupus erythematosus: auto-immune to multiple tissues
active immunity is exposed by
antigen
infection with attenuated organisms
passive immunity
infusing antibodies or activated T cells from an immune individual (breast milk)
allergy and hypersensitivity
- T cell-mediated (delayed): poison ivy, nickel allergies. ** Usually cutaneous; can occur in lungs with airborne antigens
- IgE mediated (immediate): In typical allergies, a single mast cell/basophil can bind 500,000 IgE molecules
anaphylaxis
- systemic, potentially fatal
- widespread vasodilation
- increased capillary permeability, volume loss
- leukotrienes → bronchospasm and wheezing
- treatment: epinephrine and antihistamines
Uticaria
- localized vasodilation and red flare
- increased permeability and swelling “hives”
- treatment: antihistamines
hay fever
- histamine-mediated
- vascular dilation in the nasal passages and sinuses (and eyes)
- leakage of fluid
- sneezing
- treatment: anti-histamines, local corticosteroids
asthma
- mediated by leukotrienes
- sustained bronchospasm
- treatment: B agonists, inhaled steroids, leukotriene receptor blockers, treat upper airway component
transfusion RBC’s
- packed red cells
- increase O₂ carrying capacity
- one unit increases hematocrit 〜3%
transfusion platelets
- single donation or apheresis
- one unit raises platelet count 6-8,000/mL
- indication < 50,000/mL, prior to surgery or with active bleeding
transfusion FFP
- single donation or apheresis
- usually for coagulation deficiency
- solvent/detergent plasma inactivates viruses
transfusion cryoprecipitate
clotting factors
Early transfusions
- red cell agglutination and lysis
- severe transfusion reactions, often fatal
- in other cases, well-tolerated and beneficial
- led to the discovery of RBC antigens and the practice of cross0matching
- > 30 common antigens, many rare ones
the ABO system
- ** RBC surface antigens: glycolipids or glycoproteins
- agglutinogens: surface antigens (A,B)
genes: A, B, O (maternal, paternal alleles) →genotypes: OO, OA, OB, AA, BB, AB - agglutinins (immunoglobulins): anti-A, and anti-B: begin developing age 2-8 months, peak age 10 years. response to A and B antigens in foods, and bacteria; initial exposures are environmental
transfusion reactions: agglutination
- RBC’s agglutinate
- plug small vessels
- physical distortion, phagocytic attack → hemolysis
- in some cases, immediate, complement-dependent hemolysis
The Rh(rhesus) antigens
- requires prior exposure to incompatible blood
- six common antigens (“Rh factors”) C, D, E, c, d, e
- D (“Rh positive”) is prevalent (85% EA, 100% Africans) and particularly antigenic
- C and E can also cause transfusion reactions, generally milder
Hemolytic disease of the newborn (erythroblastosis fetalis)
- ABO incompatibility ( O mother and A/B fetus): unusual, most anti-A is IgM, does not cross
- Rh incompatibility (RhD+ fetus and Rh- mother):
erythroblastosis fetalis, maternal antibodies cross the placenta and cause agglutination and lysis of fetal erythrocytes
fetal macrophages covert hgb to bilirubin → jaundice
anemic at birth; continued hemolysis for 1-2 months
may have permanent neurologic damage from the deposition of bilirubin in neural tissues (“kernicterus”)
Hemolytic disease of the newborn: treatment
- repetitive removal of Rh-positive blood, replacement with Rh-negative (400 mL exchange over 90 mins)
- may be done several times over a few weeks
- maternal antibodies disappear over 1-2 months so newborn’s Rh positive cells cease to be a target
incompatibility: transfusion reactions
- occurs because of mismatched blood
- recipient antibodies react against donor antigens
- either immediate or delayed agglutination and hemolysis
- fever, chills, SOB; potentially shock, renal shutdown
- macrophages produce bilirubin
- with normal liver function, no jaundice unless > 400 mL blood hemolyzed in < 1 day
acute renal failure after transfusion reaction
- products of hemolysis cause powerful renal vasoconstriction
- immune-mediated circulatory shock
- free hgb can leak through glomerular membranes into tubules → High quantities may block tubules
- may require acute or even chronic hemodialysis
autograft
graft obtained from same individual
isograft
graft obtained from an identical twin
graft acceptance/rejection
- autografts & isografts - obstacles are mechanical attachment and adequate blood supply
- allografts - antigenic matching is important
- xenografts - almost always rejected with tissue death 1 day to 5 weeks after grafting
successful allografts: skin, heart, liver, kidney, lung, pancreas, bone marrow, lasting up to 15 years or more
allograft
graft obtained from another individual/same speicies
xenograft
graft obtained from an entirely different species
rejection:
- hyperacute rejection - Days
- acute rejection - weeks
- chronic rejection - months to years
rejection is mainly due to activated T cells (predominantly helper T cells)
avoidance or suppression of rejection
tissue typing:
- blood type
- HLA (MHC) antigens: encoded by the MHC, seek the best match possible among the closest relative possible
- immunosuppressive drugs
immunosuppressive drugs
- glucocorticoids - suppress the growth of lymphoid cells; reduce the production of antibodies and activated T cells
- drugs that are toxic for lymphocytes - exp. azathioprine
- T cell specific agents - anti-lymphocyte globulin, cyclosporin, FK506 (tacrolimus), mycophenolate
transformative, preventing graft rejection while leaving much of the immune system intact
immunosuppression: challenges
- overwhelming infection, particularly viral infection
- reduced tumor surveillance and increased incidence of cancer
hemostasis: prevention of blood loss
- vascular constriction
- formation of a platelet plug
- formation of a blood clot
- healing of vascular damage +/- re-canalization
vascular constriction
- myogenic spasm
- local autocoid factors from damaged tissued and platelets
- nervous reflexes
- smaller vessels: thromboxane A₂ released by platelets
platelets
- 〜300,000/mm³
- 1-4 micrometers discs
- released by fragmentation of mogakaryotes
- 150-300,000 per microliter
- replaced every 10 days
- half-life of 8 to 12 days
platelet functions
- contractile compatibilities
- actin, myosin, thrombasthenin
- residual ER and Golgi: synthesize enzymes, prostaglandins, fibrin-stabilizing factor, PDGF, store Ca⁺
- mitochondrial / enzymes: produce ATP, ADP
platelet membranes:
- surface glycoprotein: repels intact endothelium, adheres to injured endothelium and exposed collagen
- membrane phospholipids: activate blood clotting
formation of the platelet plug
- contact with damaged endothelium: assume irregular forms, contract and release granules
- adhere to collagen and vWF
- other platelets accumulate, adhere, and contract, form plug, initiate clotting
- very low platelets → petechiae, bleeding gums
clot formation and progression
- begins in 15-20 seconds in severe vascular trauma
- occlusive clot within 3-6 minutes unless very large vascular defect
- 20-60 mins: clot retraction
- 1-2 weeks: invasion by fibroblasts, organization into fibrous tissue
fibrin production
- thrombin (weak protease) cleaves four smaller peptides from fibrinogen → fibrin monomer → spontaneous polymerization
- long fibers form clot reticulum
- fibrin stabilizing factor: in plasma and released from platelets, activated by thrombin, covalent cross-linking of fibrin monomers and adjacent fibrin fibers
clot extension
- thrombin is bound to platelets and trapped in the clot
- can act on prothrombin to generate more thrombin (+ FB)
- thrombin also produces more prothrombin activator by acting on other clotting factors
- additional fibrin monomers and polymers are generated at the periphery of the clot
clot retraction
- begins within 20-60 mins
- fibrin binds to the damaged vessel wall
- platelets bind to multiple fibrin fibers: contract via actin, myosin, thrombosthenin
- clot tightens, expressing serum, and slowing the vascular defect
extrinsic pathway
trauma to the vessel wall and adjacent tissues
can be explosive, with clotting in < 15 seconds
intrinsic pathway
trauma to the blood or exposure of the blood to endothelial collagen
much slower, 1-6 mins
both pathways involve
clotting factors - mostly inactive proteases that are activated in cascades
tissue injury →
- tissue factor activates the extrinsic pathway
- exposure of factor XII and platelets to collagen activates the intrinsic pathway
prevention of clotting
- smoothness of the endothelial cells
- mucopolysaccharide coating (glycocalyx) repels platelets and clotting factors
- thrombomodulin bound to endothelium binds (competes for) thrombin
- thrombin-thrombomodulin activates Protein C → inactivates factors V and VIII
- negative feedback: fibrin fibers bind 85-90% of thrombin and localize it to the clot, antithrombin III combines with the remainder and inactivates it over 12-20 mins
heparin
- physiologically, availability is limited
- used therapeutically
- highly negatively charged
- binds anti-thrombin III and increases its effectiveness 100- to 1000-fold
- heparin-antithrombin III removes free thrombin from the blood almost instantly
- also removes XIIa, XIa, Xa, and Ira
- mast cells, basophils particularly abundant in pericapillary regions of the liver and lung
*** Effect of heparin-induced thrombosis? (HIT)
immune reaction against heparin that forms large formation of clots → Platelets get reduced in this process, so it causes thrombocytopenia
clot lysis
- plasminogen is trapped in the clot
- over several days, injured tissues release tissue plasminogen activator (tPA)
- plasminogen is activated to plasmin, a protease resembling trypsin
- plasmin digests fibrin fibers and several other clotting factors
- often results in the reopening of repaired small blood vessel
key events in hemostasis
- severed vessel
- platelets agglutinate
- fibrin appears
- fibrin clot forms
- clot retraction occurs
causes of excessive bleeding
- hepatocellular disease
- vitamin k deficiency
- hemophilia
- low platelet count
vitamin K
- produced in the intestine by bacteria
- fat-soluble: malabsorption of fats can lead to deficiency
- lack of bile production or delivery can cause fat malabsorption and vitamin k deficiency
- in patients with liver or biliary disease, vitamin K can be injected 4-8 hrs before surgery
vitamin K deficiency
- essential to carboxylate glutamic acid in five important clotting factors: prothrombin and factors VII, IX, X, and protein C
- in this process, vitamin K is oxidized and inactivated
- vitamin K epoxide reductase complex 1 (VKOR c1) reduces vitamin K and reactivates it
Hemophilia A
- deficiency of factor VIII
- 85% of hemophilia cases
- 1/10,000 males
Hemophilia B
- deficiency of factor IX
- 15% of cases
- about 1/60,000 males
both hemophilia’s
- both impair intrinsic pathway activation
- both genes on the X chromosome (males only get 1 copy)
- clinically: bleeding after minor trauma
Factor VIII deficiency
- factor VIII has two components
- large & small
- deficiency of the small component causes hemophilia A → treat bleeding with factor VIII replacement
- deficiency of the large component causes von Willebrand disease (resembles decreased platelet function)
throbocytopenia
- low number of platelets
- bleeding from small venules or capillaries
- petechiae, thrombocytopenic purpura
- often idiopathic: < 50,000 = modest bleeding, < 10,000 = life-threatening
- treated with platelet infusions → effective for 1-4 days each time
Thrombus
- an abnormal clot is a thrombus, when it floats its an embolus
- caused by: endothelial roughening (exp. atherosclerosis), slow flow (exp. prolonged air travel)
- treatment: tPA, embolectomy
pulmonary embolus
- usually from deep leg veins
- part of the thrombus disengages 〜10% of the time
- occludes pulmonary arteries - potentially fatal
- tPA can be life-saving
clinical useful anticoagulants: heparin
- binds, and potentiates antithrombin III
- works rapidly, generally used acuteley
clinical useful anticoagulants: Coumadins
- inhibit VKOR c1
- deplete active vitamin K → deplete active prothrombin, factors VII, IX, X
- slower acting (days); used chronically
clinical useful anticoagulants: In vitro anti-coagulation
- siliconized containers prevent activation of factor VII and platelets
- heparin - used in blood collection, heart-lung and kidney machines
- calcium chelators (citrate, EDTA) used in blood collection, blood storage
prothrombin time
- add excess calcium and tissue factor to oxylated blood, measure time to clot
- assesses extrinsic and common pathways **
- usually about 12 seconds
- tissue factor batches have to be standardized (activity expressed as “international sensitivity index (ISI)”
