Alterations of Erythrocyte Function Flashcards
anemia =
a reduction in the total circulating red cell mass or a decrease in the quality or quantity of hemoglobin
too many RBCs is called
polycythemia
normal RBC count; normal HGB
HGB: 12-18g/dL
RBCs: 4.2-6.1 x 10^6 /mcl
Excessive destruction of RBCs caused by two types of hemolysis…
HEREDITARY HEMOLYSIS - sickle cell trait or disease
ACQUIRED HEMOLYSIS :
- immune reaction (blood transfusion)
- infection (malaria, clostridial)
- drugs (quinidine, PCN, methyldopa)
- liver or kidney disease
- toxins (chemical, venoms)
Classifications of anemia include 3 things?
-ETIOLOGIC FACTOR (cause) - ex. iron-deficient
-SIZE:
.Identified by terms that end in -CYTIC
.macrocytic (large), microcytic (small), normocytic (normal)
-HEMOGLOBIN CONTENT
.identified by terms that end in -CHROMIC
.normochromic (normal amount), hypochromic (decreased amount)
RBCs are present in various sizes
ANISOCYTOSIS
RBCs are present in various shapes
POIKILOCYTOSIS
Classic symptoms of anemia?
fatigue, weakness, dyspnea, elevated HR, pallor - remember organ dysfunction can also occur
Normal hgb males; normal hgb females
M = 13-17 F= 12-15
HCT levels M & F?
M - 41-50%
F - 35-46%
characterized by RBCs that are abnormally small and contain reduced amounts of Hgb
microcytic-hypochromic anemias
Most common microcytic-hypochromic anemia worldwide?
iron-deficiency anemia (IDA)
Highest risk for IDA? Associated with what in children? Causes?
Risk: older adults, women, infants, and those living in poverty
Children: cognitive impairment
Causes: inadequate diet, blood loss, chronic parasite infection, metabolic or functional iron deficiency, menorrhagia
Most common PHYSIOLOGIC CAUSE of IDA?
menstruation - normal menstrual flow = 50mL but can vary by 5x
Woman with increased menstrual loss require increased intake _________/day which equals dietary consumption of _______
3-4mg/day which equals dietary consumption of 30-40mg/day
For MEN AND POSTMENOPAUSAL WOMEN, IRON DEFICIENT ANEMIA IS A GOOD INDICATOR of what?
MALIGNANCY
10-17% will be from malignancy
*older age, male, elevated LDH, low ferritin
(LDH indicates tissue damage)
Most common pathophysiologic cause of IDA?
GI bleed
Protein that STORES IRON. Where is it produced? Where is most of it found? Small amounts where?
FERRITIN - produced in the intestines, but found mostly in the liver, spleen, and bone. Small amount circulates in the blood.
What is the MOST SENSITIVE TEST FOR IDA?
ferritin levels
TRANSPORTS IRON IN THE BLOOD
TRANSFERRIN
*delivers iron from absorption centers (duodenum, macrophages) to tissues
How is iron saturation of transferrin measured? Direct or indirect?
TYPICALLY MEASURED INDIRECTLY BY ASSESSING THE TOTAL IRON BINDING CAPACITY (TIBC)
MEASURE OF AVAILABLE TRANSFERRIN THAT IS LEFT UNBOUND TO IRON
WHAT IS CONSIDERED HIGH?
*see slide 12-13
TOTAL IRON BINDING CAPACITY (TIBC)
LOW TRANSFERRIN THAT IS ACTUALLY SATURATED WITH IRON = HIGH TIBC (meaning that not much transferrin is actually saturated)
*THIS MEANS THERE IS MORE CAPACITY TO BIND OR HIGH TOTAL IRON BINDING CAPACITY
In iron deficiency anemia is the ferritin high or low?
What would happen to the total iron binding capacity in iron deficiency?
ferritin is low (classic test for IDA)
TIBC is high or increased b/c the liver produces more transferrin b/c it’s trying to maximize whatever iron is there to be delivered to the tissues that need it.
This means there are more binding sites for iron
Increased transferrin total, but decreased transferrin saturation = high TIBC
Diagnostic manifestations of IDA?
VALUES: MCV, MCH, RDW, FERRITIN, NORMAL SERUM IRON?, TIBC?
Reticulocyte count?
- low MCV = microcytic
- low MCH = hypochromic
- high RDW >15
- Low INITIAL reticulocyte count
- Elevated reticulocyte count once tx and supplementation with iron begins (can be high after tx)
- FERRITIN LOW
- LOW SERUM IRON (NORMAL 50-75MCG/DL)
- TIBC HIGH (MEANING THAT TRANSFERRIN SATURATION IS DECREASED)
Moderate anemia hgb level is?
7-11: mod s/s
s/s of IDA
palpitations, dyspnea, exercise intolerance, angular stomatitis, pallor, Koilonychia (spoon nails), pica
severe IDA hgb less than and s/s
7 - s/s postural hypotension, dizziness, weak, gastritis, paresthesias, lethargy
caused by a DEFECT IN MITOCHONDRIAL HEME SYNTHESIS - what type of anemia? and what does it show on smear - type of RBCs?
SIDEROBLASTIC ANEMIA, which is a microcytic-hypochromic anemia
what causes sideroblastic anemia? how is it diagnosed?
altered mitochondrial metabolism causes ineffective iron uptake and results in DYSFUNCTIONAL HEMOGLOBIN SYNTHESIS
- intracellular iron accumulates
- can be d/t ETOH abuse, lead poisoning
- ringed sideroblasts found in the BM are diagnostic (RBC w/iron granules that have not be synthesized into hgb)
Autosomal recessive blood disorder that causes MICROCYTIC HYPOCHROMIC anemia
THALASSEMIA
what diagnostic test tests for thalassemia?
diagnostic test is hgb electrophoresis
what is thalassemia characterized by? and what does it result from?
what does this cause?
characterized by ABNORMAL FORMATION OF HGB
results from a MUTATION THAT CAUSES LOSS OF ONE OR BOTH OF ALPHA GLOBIN CHAINS OR ONE OR BOTH OF BETA GLOBIN CHAINS
abnormal hgb formed results in IMPROPER OXYGEN TRANSPORT AND DESTRUCTION OF RBCS; RESULT IN ANEMIA
what kind of anemia results from thalassemia? what does it look like? what kind of complications? what might be seen?
MICROCYTIC HYPOCHROMIC (low MCV, low MCHC)
TARGET CELLS may be seen
complications include iron overload - bone deformities, and CV illness.
*possible protection from malaria
see chart slide 20 - IDA vs thalassemia
ferritin level? serum iron? TIBC? MCHC? hgb electrophoresis? ethnic background?
…
clinical features of sideroblastic anemia? hct? MCV? serum iron? transferrin saturation high or low?
- hct - 20-30%
- MCV usually normal, can be increased or decreased
- serum iron is elevated
- transferrin saturation is high - meaning that TIBC is lower (normal or borderline is what chart says)
can cause iron overload (hemochromatosis) or enlarged spleen and liver
what are the megaloblastic anemias? Macrocytic-normochromic
folate, B12 deficiency, poisons, some antiviral drugs and some chemo
What causes macrocytic-normochromic (megaloblastic) anemias?
PATHO: DEOXYRIBONUCLEIC ACID (DNA) SYNTHESIS IS DEFECTIVE DUE TO DEFICIENCIES IN VITAMIN B12 OR FOLATE
RBCs do not form sufficiently and are released prematurely
Vitamin B12 (cobalamin) comes from? And what does it do in the body - 3 things?
-all b12 comes from diet: flies, walks, swims
FUNCTIONS:
- KEEPS NERVOUS SYSTEM FUNCTIONING PROPERLY
- NECESSARY IN THE FORMATION OF BLOOD
- INVOLVED IN METABOLISM OF EVERY CELL BUT ESPECIALLY AFFECTING DNA SYNTHESIS AND REGULATION
Where is B12 stored?
stored in liver - 2000 to 5000mcg and can take up to 3 years to deplete
very unusual to develop B12 deficiency due to diet except if a strict vegetarian
Lab findings in B12 cabalamin deficiency?
MCV? MCH? Peripheral blood smear? Reticulocyte count? BM?
- MCV is usually very high
- MCH is normal
- Peripheral blood smear: anisocytosis (RBCs are unequal in size), poikilocytosis (RBCs are different shapes), macro-ovalocyte (enlarged, oval shape RBC), HYPERSEGMENTED NEUTROPHILS
- low reticulocyte count initially, and then increases after supplementation occurs
- can see pancytopenia if severe
The most common type of macrocytic normochromic anemia that is CAUSED BY A VITAMIN B12 DEFICIENCY? what causes this?
PERNICIOUS ANEMIA
LACKS INTRINSIC FACTOR FROM THE GASTRIC PARIETAL CELLS
REQUIRED FOR VITAMIN B12 ABSORPTION
PERNICIOUS ANEMIA COULD BE D/T A ________ OR _______ DISORDER
CONGENITAL OR AUTOIMMUNE
*AUTOANTIBODIES AGAINST INTRINSIC FACTOR WHICH IS RELEASED FROM PARIETAL CELLS in the fundus of the stomach (antiparietal antibodies)
clinical manifestations of pernicious anemia
THREE MOST IMPORTANT?
weakness, fatigue, PARESTHESIAS of the feet and fingers, loss of appetite, abdominal pains, wt loss, sore tongue that is smooth and beefy red secondary to ATROPHIC GLOSSITIS, “LEMON YELLOW” SALLOW skin as a result of a combination of pallor and icterus…
*yellow skin d/t weak RBCs that break down more quickly which causes release of bilirubin by the liver
neurologic symptoms from nerve demyelination - ataxia, decreased or lack of DTRs, pathological reflexes; babinski’s, severe paresis (NOT reversible even with tx)
Schilling Test
Testing:
▪ Schilling test: localized site of pathology of the B12 deficiency
▪ Give IM B12, PO radioactive B12 – normal pt’s with extrinsic factor should absorb radioactive B12 and excrete in urine because the receptors would be saturated with IM B12; if there is a problem with the intrinsic factor then it will not be present in the urine; test is repeated and exogenous intrinsic factor is given
*remember that without intrinsic factor B12 can not be absorbed into the bloodstream, hence it would never make it to the kidneys to be excreted
Folate (folic acid) deficiency anemia
What is folate required for?
Where does absorption occur?
Common in what population?
Associated with?
- Folate is an essential vitamin for RNA & DNA synthesis
- absorption of folate occurs in the upper SI, and is not dependent on any other factor
- is common in alcoholics and people with chronic malnourishment
- associated with neural tube defects of the fetus
In what foods do you find folic acid? What is the daily requirement? Most common cause of deficiency?
fruits & veggies (esp citrus fruits + leafy greens)
Daily requirement 50-100mcg
Most common cause of deficiency = diet
-alcoholics, anorexics, overcooked foods, diets that exclude fruits/veg
Clinical manifestations of folic acid deficiency?
(remember folic acid is the manmade version)
What is usually NOT seen?
- SEVERE CHEILOSIS: scales and fissures of the lips and corners of the mouth
- STOMATITIS: mouth inflammation - painful ulcerations of the buccal mucosa and tongue: characteristics of burning mouth syndrome
- DYSPHAGIA (difficulty swallowing), flatulence, and watery diarrhea
- Neurologic symptoms: USUALLY NOT SEEN
- SOME SIMILARITIES TO B12 MINUS NEUROLOGICAL
Folic acid lab findings? What type of anemia - what do RBCs look like? MCV high or low? Peripheral blood smear? Serum folic acid?
Macrocytic-normochromic anemia
MCV - high
MCH - normal
Blood smear: anisocytosis, poikilocytosis, macro-ovalocyte, HYPERSEGMENTED NEUTROPHILS (same as B12)
*ABNORMALLY LOW SERUM FOLIC ACID <150 ng/mL and serum B12 is normal
Person with gastrectomy and difficulty walking (neuro symptom), abdominal pain, etc. Nurse suspects what?
pernicious anemia d/t loss of parietal cells and intrinsic factor
ALCOHOL INDUCED MACROCYTIC ANEMIA
Interferes with absorption of what? What happens to RBC?
Interferes with ______ synthesis: sideroblastic anemia
Interferes with _______
Interferes with absorption of folic acid (megaloblastic)
Interferes with Hgb synthesis: (sideroblastic anemia)
Interferes with erythropoiesis (megaloblastic)
*anemia reverses with abstinence from EtOH w/i weeks
Characterized by RBCs that are relatively normal in size and Hgb content but insufficient in number - no common cause, and happen less frequently than other anemias
normocytic-normochromic anemias
List of normocytic-normochromic anemias
- aplastic anemia
- posthemorrhagic anemia
- hemolytic anemia: autoimmune, drug-induced, sickle cell
- anemia of chronic disease
List of macrocytic-normochromic anemias?
- vit B12 (cobalamin) deficiency
- pernicious anemia (most common)
- folic acid deficiency
- alcohol induced
List of microcytic-hypochromic anemias
- IDA
- Sideroblastic anemia - dysfunctional hemoglobin synthesis
- Thalassemia - autosomal recessive, electrophoresis, mutation causes loss of one or both of alpha globin chains or one or both beta chains, target cells
APLASTIC ANEMIA results in? what causes most of the time? Pathophysiology? S/s? Evaluate for how?
- pancytopenia - reduction or absence of all three types of blood cells
- most are autoimmune, but some are r/t exposure to benzene, arsenic, and chemo drugs
- HYPO-CELLULAR BM THAT HAS BEEN BEEN REPLACED WITH FAT
- s/s: hypoxemia, pallor (w/brown skin sometimes), weak, fever, dyspnea, hemorrhage if platelets are affected
- evaluate using BM biopsy
A person is admitted with an autoimmune disease directed against the hematopoietic stem cells. The nurse knows this will produce?
aplastic anemia - pancytopenia
Anemia caused by ACUTE blood loss from the vascular space?
POSTHEMORRHAGIC ANEMIA
associated with destruction of RBC type of anemia. two types?
HEMOLYTIC ANEMIA
can be intrinsic (most often hereditary) - caused by intracorpuscular defects. Sickle cell.
can be extrinsic (extracorpuscular defects) - immune, infection, drugs, hypereactive spleen, etc.
a type of anemia that is BASED ON THE OPTIMAL TEMPERATURE OF WHICH THE AUTO-ANTIBODY BINDS TO THE ERYTHROCYTE
AUTOIMMUNE HEMOLYTIC ANEMIA
Form of immune hemolytic anemia that is usually the result of an allergic reaction against foreign antigens (PCN, cephalosporins)
DRUG-INDUCED HEMOLYTIC ANEMIA
Clinical manifestations of hemolytic anemia
may be asymptomatic, splenomegaly, jaundice (icterus)
G6PD deficiency caused by? What happens?
glucose-6-phosphate dehydrogenase
caused by hereditary enzyme defect (x-linked)
lack of NADPH in pentose pathway decreases protection against oxidants - development of Heinz bodies that damage the cell membrane
People with G6PD only have hemolysis when?
WITH OXIDATIVE STRESS (infection or drug exposure)
episodes are self-limiting
lab findings with G6PD
b/w episodes? during episode? assay?
normal b/w episodes
during episode: reticulocytosis (increase in number of immature RBCs), increased indirect (unconjugated) bilirubin (jaundice), bite cells, blister cells, Heinz bodies
G6PD assay? may be low, but misleading at or directly after episode when the enzyme deficient group of cells has been removed
*should repeat several weeks after hemolysis resolves (6-8 wks)
Hemolytic anemia - sickle cell anemia
mutation of?
homozygous for mutation?
heterozygous for mutation?
autosomal recessive
mutation of B globin chain of Hgb
*hemoglobin A replaced with HbS - sickled hemoglobin
those HOMOZYGOUS have sickle cell anemia (HbSS)
those who are HETEROZYGOUS for mutation have sickle cell trait (HbAS)
1/10 AA will have trait
1/500 AA will have disease
HgbS is unstable and when exposed to acidosis or oxidative stress (hypoxia) what occurs?
How long do sickled cells survive?
the cell sickles and sickling is permanent (however from my research they go back and forth several times before this is permanent)
sickled shape prevents them from passing through narrow capillaries
10-20 days of survival
Lab findings sickle cell anemia
- peripheral smear
- hct, hgb, reticulocytes, wbc
- what confirms dx?
Hct 20-30%
Hgb 8-10
peripheral smear: SICKLED CELLS, TARGET CELLS, HOWELL-JOLLY BODIES
- reticulocytosis, nucleated RBC, WBC elevated 12-14K
- DX CONFIRMED BY HGB ELECTROPHORESIS - in homozygous: HgbS will be predominant, no HgbA
s/s of sickle cell anemia
how long do episodes last?
what can vaso occlusion cause?
- painful attacks d/t infection, dehydration, hypoxia
- jaundice (hemolysis)
- pigment gallstones
- spenomegaly/infarcted spleen
- poor healing ulcers on lower tibia
- severe anemia
- hemolytic, aplastic crisis
- episodes last hrs to days
- occlusion: CVA, organ damage, osteonecrosis, renal tubular concentrating defect, retinopathy, pul. HTN, acute chest crisis, splenic sequestration crises (pooling of blood in spleen + circulatory collapse)
RBCS BECOME SENSITIVE TO COMPLEMENT WHICH CAUSES LYSIS
what occurs?
PNH - paroxysmal nocturnal hematuria
*an acquired stem cell disorder
pts have episodic hematuria, typically brown urine in am
anemia varies in severity
r/f thrombosis
PNH tests
best test?
urine hemosiderin is useful
best test is flow cytometry - CD59 and CD55 will be deficient on RBC
Most common anemia in elderly - begins as a normocytic anemia and progresses to microcytic when advanced
ANEMIA OF CHRONIC DISEASE
- erythrocytes TYPICALLY normocytic, normochromic
- 1/3 of patients will have microcytic anemia
Pathophysiology of anemia of chronic disease
Likely secondary to chronic inflammatory response that results in low access of iron in circulation
*decreased erythropoieses: decreased RBC & decreased availability of iron
ACD - anemia of chronic disease diagnostic manifestations?
TIBC
Ferritin?
Transferrin saturation
BM?
Dysfunctional iron utilization. IRON ISN’T STORED PROPERLY instead of being released to tissues that need it. Inflammatory response –> chemicals released –> iron is trapped –> dysfunctional iron utilization. Decreased RBC lifespan, suppressed production of EPO, altered metabolism
TIBC is low or normal
Ferritin is normal or high
Transferrin saturation CAN be very low (misleading to dx of IDA. not a good indicator)
BM - can distinguish b/w IDA and ACD
ACD mild-to-moderate anemia from decreased erythropoiesis
Diseases that cause?
s/s like what other type of anemia?
AIDS, malaria, RA, lupus, hepatitis, renal failure, malignancies
d/t decreased RBC lifespan, suppressed production RBCs, ineffective BM response to EPO, altered iron metabolism
like IDA
Anemia of chronic disease is caused by?
1- IgG binding to RBC at normal body temperatures
2-autoantibodies against RBC surface antigen
3-reduced response to EPO
4-paroxysmal nocturnal hemoglobinuria
3- reduced response to EPO
overproduction of RBCs
remember that relative _____ can occur with what?
polycythemia
dehydration - resolved with fluid intake
RBC production occurs in the _____ under the stimulation of _______
BM under stimulation of EPO
myeloproliferative disease that increases production of RBCs and is a primary form of the disorder
POLYCYTHEMIA VERA
POLYCYTHEMIA VERA CAUSES OVERPRODUCTION OF?
RBCS (FREQUENTLY WITH INCREASED LEVELS OF WBCS (LEUKOCYTOSIS) AND PLATELETS (THROMBOCYTOSIS)
It is a type of blood cancer
what mutation causes polycythemia vera?
what would happen to EPO with this disease?
is caused by an ACQUIRED MUTATION IN JANUS KINASE 2 (JAK2)- this promotes the growth and division (proliferation) of cells
- NEGATES THE SELF-REGULATORY ACTIVITY OF JAK2 THAT ALLOWS THE EPO RECEPTOR TO BE CONSTITUTIVELY ACTIVE, REGARDLESS OF THE LEVEL OF EPO
- if RBC count is inappropriately high, this should cause negative feedback on EPO, and thus EPO LEVEL IS LOW IN PV
Secondary polycythemia - and how can it occur? what causes it? Is EPO high or low?
ELEVATED EPO
- can occur either as a normal response to needing more RBCs or from an overproduction (eg by a tumor)
- chronic lung disease, living at high altitude, chronic monoxide exposure, sleep apena, etc. (chronic hypoxia) causes it
Lab findings with secondary polycythemia? Tumor or normal response to hypoxia
hct and hgb elevated
EPO INCREASED IF THERE IS AN ECTOPIC SOURCE OF EPO OR IF POLYCYTHEMIA IS SECONDARY TO HYPOXIA
*remember EPO decreased in polycythemia vera
myeloproliferative RBC disorders list
- Polycythemia vera (primary)
- secondary polycythemia
- iron overload (hereditary hemochromatosis)
iron overload when primary (hereditary) is called what? what causes it? what happens?
HEREDITARY HEMOCHROMATOSIS
- common inherited, autosomal recessive disorder of iron metabolism
- increased GI iron absorption w/tissue deposition
- excess iron deposited in the liver, pancreas, heart, joints, and endocrine gland, causing tissue damage
- “bronze diabetes”
s/s of hereditary hemochromatosis? TIBC high or low? ferritin high or low?
fatigue, malaise, abdominal pain, arthralgia, and impotence
hepatomegaly, elevated liver enzymes, bronzed skin, diabetes, cardiomegaly
TIBC low or normal, ferritin elevated
state of excessive bleeding
HYPOCOAGUABLE STATE
state of excessive clotting
-what causes this?
HYPERCOAGUABLE STATE
-EXCESS OF PLATELETS OR DEFICIENCY OF ANTI-THROMBOTIC PROTEINS (PROTEIN C, S, ANTITHROMBIN III)
how do hypocoaguable states arise?
ARISE FROM EITHER DECREASED COAGULATION FACTORS, DECREASED PLATELET FUNCTION, OR DECREASED PLATELET NUMBER (THROMBOCYTOPENIA)
*leads to excessive bleeding/bruising from minor trauma
if hypocoaguable state occurs d/t platelet problem?
P,P,P - PETECHIAE, PLATELET DYSFUNCTION, LOW PLATELETS
clotting factors made in the liver need what for synthesis?
VITAMIN K (II, VII, IX, AND X)
vitamin K is necessary for synthesis and regulation of prothrombin, the prothrombin factors (II, VII, XI, X) and proteins C and S (anticoagulants)
X-LINKED GENETIC DISEASE that leads to clotting factor deficiency
HEMOPHILIA
Two types of hemophilia?
- Hemophilia A (classic) is deficiency of factor VIII
- Hemophilia B (Christmas disease) is a deficiency of factor IX (Christmas factor)
decrease in, or absence of vWF results in?
VON WILLEBRAND’S DISEASE
*RESULTS IN DECREASED ABILITY OF PLATELETS TO BIND TO VESSEL WALL
there is defect in GP-IX (on platelet and links to vWF) - so vWF is attached to damaged endothelial and then GP-IX on platelet attaches
BERNARD-SOULIER SYNDROME
results in the decreased ability of platelet to bind to vessel wall
decrease in storage pool of signaling molecules normally released by platelets
STORAGE POOL DISEASES
this slide set says that thrombocytopenia is less than what?
150,000
IgG antibody that targets platelet glycoproteins causes what? what happens?
immune (ideopathic) thrombocytopenic purpura (ITP)
antibody-coated platelets are sequestered and removed from the circulation
one of the most common childhood bleeding disorders?
*manifestations?
ACUTE FORM OF IDEOPATHIC THROMBOCYTOPENIC PURPURA (ITP) THAT OFTEN DEVELOPS AFTER A VIRAL INFECTION IS ONE OF THE MOST COMMON CHILDHOOD BLEEDING DISORDERS
s/s - petechiae, purpura, major hemorrhage
a thrombotic microangiopathy (damage to micro-vasculature)
THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP)
What happens in thrombotic thrombocytopenic purpura? TTP
s/s
PLATELETS AGGREGATE, FORM MICROTHROMBI, AND CAUSE OCCLUSION OF ARTERIOLES AND CAPILLARIES
classic fever, purpura, altered mental status, neuro signs, renal problems, thrombocytopenia, hemolytic anemia
same underlying pathophysiology as TIP, but _____ IS GENERALLY R/T SYNDROME THAT OCCURS FOLLOWING DIARRHEAL ILLNESS (E.COLI, SHIGELLA) AND IS MORE COMMON IN CHILDREN
HEMOLYTIC UREMIC SYNDROME (HUS)
ESSENTIAL (PRIMARY) THROMBOCYTHEMIA (THROMBOCYTOSIS)
characterized by how many platelets?
what occurs in this condition?
what happens as a result?
can occur with?
> 600,000
myeloproliferative disorder of platelet precursor cells - megakaryocytes in the BM are produced in excess
micro-vasculature thrombosis occurs
*can occur w/polycythemia vera or inflammatory diseases
Liver disease can cause
defects in coagulation, fibrinolysis, platelet number and function
Complex, acquired disorder in which CLOTTING AND HEMORRHAGE SIMULTANEOUSLY OCCUR
DISSEMINATED INTRAVASCULAR COAGULATION (DIC)
DIC is caused by?
infection, massive trauma or surgery, neoplastic disease, chronic inflammatory disease, complication of child birth
What is DIC the results of? ENZYME?
DIC IS THE RESULT OF INCREASED PROTEASE ACTIVITY IN THE BLOOD CAUSED BY UNREGULATED RELEASE OF THROMBIN WITH SUBSEQUENT FIBRIN FORMATION AND ACCELERATED FIBRINOLYSIS. CLOTTING FACTORS BECOME DEPLETED
DIC - by activating the fibrinolytic system (plasmin), the patient’s what will increase?
fibrin degradation product (FDP) and D-dimer levels will increase
DIC s/s
bleeding, purpura, petechiae, symmetric cyanosis of toes and fingers
Protein _____ and what else serve as checks and balances in the clotting system
what occurs if there is a mutation in these?
PROTEIN C, S, AND ANTITHROMBIN III SERVE AS CHECKS AND BALANCES IN CLOTTING TO PREVENT THROMBOSIS
(normally work as anticoagulants)
IF THERE IS A MUTATION - THIS LEADS TO DEFICIENCY = TENDENCY TO CLOT
______ antibodies predispose to HYPERCOAGULABILITY
in what disease do you sometimes see these?
ANTI-PHOSPHOLIPID ANTIBODIES
-Lupus
mutation with factor V causes what?
how is it inherited?
hypercoaguable states of Factor V Leiden
AUTOSOMAL DOMINANT DISORDER
incomplete penetrance occurs - many who carry the mutation do not suffer any consequences
What occurs with factor V Leiden?
WHERE DOES IT USUALLY OCCUR?
CAUSES FACTOR V TO BE UNABLE TO BE INACTIVATED BY PROTEIN C, SO CLOTTING IS ENCOURAGED
EXCESSIVE CLOTTING IS ALMOST ALWAYS RESTRICTED TO THE VEINS
PROTEIN C DEFICIENCY is a type of?
Increased risk for? but no association with?
TYPE OF THROMBOPHILIA
INCREASED R/F VENOUS THROMBOEMBOLISM
NO ASSOCIATION WITH ARTERIAL THROMBOTIC DISEASE
What does protein C deficiency cause in newborns?
PURPURA FULMINANS
*2 abnormal copies of gene leads to absence of functioning protein C in blood
Protein S deficiency causes what?
What is protein S?
hypercoagulable state
Protein S is vitamin K dependent anticoagulant that normally activates protein C in degradation of factor Va and Factor VIIIa
DEFICIENCY LEADS TO IMPAIRED FUNCTION/ACTIVITY OF PROTEIN S AND ULTIMATELY DECREASED DEGRADATION OF THESE FACTORS
THUS THERE IS INCREASED R/F VENOUS THROMBOSIS
can be acquired from vitamin K deficiency, or tx w/warfarin
