Hematology Flashcards
What is the composition of plasma?
Water (92%)
Nutrients such as glucose, proteins, fats, and electrolytes
Contains albumin and other transport proteins, immunoglobulins, clotting factors, and enzymes
Contains small amounts of dissolved CO2 and oxygen (not bound to hemoglobin)
What is plasma serum?
Plasma minus the clotting factors; specimen is not antio-coagulated
What are acute phase reactants?
defined as proteins that change their serum concentration by >25% in response to inflammatory cytokines (IL-1, IL-6, TNFα)
What system are the acute phase reactants a part of?
Innate immune system
What can APRs play a role in mediating?
Fever, leukocytosis, thrombocytosis, increased cortisol, decreased thyroxine, and decreased serum ion
Positive APRs
C reactive protein Fibrinogen (ESR) complement globulin D-dimer prothrombin factor VIII vW factor ferritin hepcidin ceruloplasmin haptoglobin alpha-1 antitrypsin platelets
Negative APRs
albumin pre-albumin transferrin antithrombin transcortin retinol-binding protein transthyretin
What lab test is used as a marker for inflammation in the body?
ESR
White blood cells include?
Granulocytes, Monocytes, and Lymphocytes
What are the three granulocytes?
Neutrophils, eosinophils, and basophils
What are platelets derived from?
Megakaryocytes
What are band cells?
Immediate precursor to the mature granuloctyes
What is the main component of RBCs?
Hemoglobin
4 pyrrole rings equals what?
1 protoporphyrin complex
1 protoporphyrin complex + 1 atom of reduced iron equals what?
1 heme unit
4 heme units + 4 globulin polypeptides (1 heme unit per globulin polypeptide) equal what?
1 molecule of hemoglobin
After separating from the iron ion, the cleaved protoporphyrin complex gives rise to what?
bilirubin
What is a CBC?
Complete Blood Count- automated reading in the lab that gives numbers and percentages of cells, quantifies RBC size, shape and color among other indices
What is the most abundant blood cell type?
RBC
Where are microcytic cells seen?
Iron deficiency and thalassemia
Macrocytic cells are seen when?
BAD Hemoglobin Level B12 and folic acid deficiency Alcoholism Down syndrome Hypothyroidism Liver disease
What is RDW?
Red cell distribution of width. If the number is high, it suggests a divergent population of red cells of different sizes
What is anisocytosis?
RBCs of different sizes
If you have pure macrocytosis what will your MVC and RDW values be?
Elevated MVC, Normal RDW
Iron deficiency anemia, what will your MVC and RDW values be?
Low MVC, Normal RDW
Mixed macroctyosis and microctyosis, what will your MVC and RDW values be?
Normal MCV, Elevated RDW
Hemolytic anemia with reticulocytes, what will your MVC and RDW values be?
Elevated MCV, Elevated RDW
Ovalocytes and elliptocytes characterize some inherited red cell abnormalities, what disease are these seen in?
hereditary elliptocytosis
Spheroctyes are seen in what diseases?
hereditary spherocytosis and autoimmune hemolytic anemia.
Schistoctyes are found when?
point to destruction within the vascular spaces. these are seen in hemolytic anemia, thrombotic thrombocytopenic purpura (TTP), disseminated intravascular coagulation (DIC), or a prosthetic heart valve.
Tear drop cells are found where?
in extramedullary hematopoiesis (EMH)
extramedullary hematopoiesis (EMH) comes into play when?
bone marrow failure.
EMH occurs in what conditions?
hemoglobinopathies, myeloproliferative disorders, or bone marrow infiltration by tumors
EMH occurs in what parts of the body?
spleen, liver, and occasionally the lymph nodes. less common organs; pleura, lungs, gastrointestinal tract, breast, skin, kidneys, and adrenal glands
EMH is part of what system of the body?
Reticular endothelial system
Macrocytic anemia will be shown in patients with what kind of deficiency?
Vitamin B12
Schistocytes are seen in what time of anemia?
Microangipathic hemolytic anemia
In hereditary spheroctyosis, there is a lack of what protein?
spectrin
What kind of protein is spectrin?
a key RBC cytoskeletal membrane protein
What test can be given in the lab to prove hereditary spherocytosis?
increased osmotic fragility
What do rouleaux RBCs look like?
stacked together long chains
When are rouleaux seen?
with increased serum proteins, fibrinogen and globulin. this is the mechanism for the erthrocyte sedimentation rate
what is the erthrocyte sedimentation rate for?
increases specifically with inflammation and increased “Acute phase” serum proteins
what are reticulocytes?
normal, immature form of the RBC. they develop and mature in the bone marrow and then circulate for about a day in the blood stream before fully maturing into RBCS
instead of a cell nucleus, what do reticulocytes have?
residual ribosomal RNA in their cytoplasm
what are howell jolly bodies?
rbc inclusion. inclusions of nuclear chromatin (DNA) remnants
what is basophillic stippling?
small dots at the periphery of red cells. the dots represent ribosomes
in what conditions is basophillic stippling seen?
lead and heavy metal poisoning, thalassemias, and alcohol abuse
what are heinz bodies and when are they seen?
denatured hemoglobin seen in G6PD deficiency
when are nucleated RBC seen?
bone marrow stress
what is one white blood cell inclusion?
dohle bodies
what are dohle bodies?
light, blue-gray oval, basophillic inclusions located in the peripheral cytoplasm of neutrophils
what are dohle bodies remnants of?
rough endoplasmic reticulum
when you see a high amount of poikilocytes, anisocytes and rbc inclusions, what does this usually mean?
spleen is not present
how many lobes in a neutrophil?
3-4 lobes
how many lobes in a eosinophil?
bilobed
how many lobes in a basophil?
3 lobed but difficult to see
what is the most abundant type of granulocyte?
neutrophils
more than 4 lobes of a neutrophil means they are what?
hyper segmented
what is the least plentiful blood cell type
leukocytes (WBCs)
how do neutrophils defend the body and when?
defend by phagoctyosis and enzymatic lysis. during infection
when do eisonophils defend the body and how?
react in allergic reactions and parasitic infection. defend by phagoctyosis and enzymatic lysis
what do basophils produce?
histamine, heparin, and IL-4
how do basophils defend?
release of chemical mediators
what do monocytes become?
macrophages
what are lymphocytes responsible for?
antibody production, cell mediated immunity, innate immunity
when are immature neutrophils seen?
during bone marrow stress. more neutrophils are produced as seen with infection, pregnancy, recovery from bone marrow suppression, and or hemotolgic malignancies
how many lobes in a band cell
uni-lobar
5 or more lobes of a neutrophil?
hyper segmented
when are hypersegmented neutrophils seen?
in megaloblastic processes (b12, folate deficiency)
a very high WBC count (>50,000) that is not leukemia, is what?
leukomoid reaction
when do you see an increased number of eosinophils?
NAACP. N- neoplastic A- asthma A- allergic reactions C- collagen vascular disease (rheumatologic) P- parasites
what is basophilia?
increase of basophils in a persons blood
when is basophillia seen?
basophilic leukocytosis; associated with leukemia
(chronic myelongenous leukemia)
hypersensitivty
inflammatory reactions
hypothyroidism
infects with; TB, some viruses, Helminthic (parasitic) infections
what do B cells do
scan the intracellular environment for foreign invaders
directly kill virally or bacterially infected cells
naturally eradicate cancer cells
activate and help other immune cells including other lymphocytes that either chaperone, ingest, or make antibodies against foreign invaders
can remember a foreign invader they encountered decades ago
natural killer cells
cells kill tumor cells and virally infected cells. scan the surface. allows them to hunt down and destroy cells that are infected or that have become cancerous.
atypical lymphocytes
larger than normal. large nucleoli. more cytoplasm.
when are atypical lymphocytes seen
infectious mononucleosis or leukemia
monocytes
largest cell in the blood. produced in the bone marrow and stored in the spleen.
what do monocytes become when they travel to the site of infection and enter tissues?
macrophages
what do monocytes do?
perform phagocytosis, antigen presentation, and cytokine production to kill microbes
what are platelets?
anuclear cells derived from megakaryocytes
second most plentiful type of blood cell
platelets
what type of substances do platelets release for wound healing?
vasoactive compounds (vasoconstrictors) and platelet chemotactic agents (cytokines)
antigens a and b are what kind of antigens
carbohydrate
2nd most important consideration in transfusion medicine
D (Rh) antigen
when should RhoGAM be given:
- after delivery of an Rh positive baby
- routine prevention of Ph immunization at 26 to 28 weeks
- maternal or fetal bleeding during pregnancy from certain conditions
- actual or threatened pregnancy loss at any stage
- ectopic pregnancy
blood components
PRBCs, platelets, and fresh-frozen plasma
risks of transfusion:
- transfusion reaction
- GVDG (graph vs. host disease: WBCs and antibodies in the donors blood attack the recipient)
- fluid overload (give furosemide)
- infection (Hep B, C, HIV, etc.)
Immature cell types
bone marrow problem
smudge cells
CLL. WBC in the process of death = apoptosis
what do blast cells usually show?
great physiological stress or tumor cells
when are smudge cells indicated?
in the presence of lymphocytic leukemia
definition of a blast cell
very immature cells with larger nuceli that contain nucleoli. indicative of acute lymphocytic leukemia
Low hb/hct indicative of:
anemia
anemia: Red cell loss
GI bleeding menorrhagia excess phlebotomy blood donation (high retic count)
anemia: inadequate production
(low retic count) absence of stimulus to produce: - low erythropoietin level in CVD - hypothyroidism - androgen deficiency lack of/abnormal raw materials: - folic acid - vitamin b12 - Fe - hemoglobinopathy intrinsic bone marrow problem: - myelofibrosis - malignancy - aplastic anemia - poisons, drugs - radiation
normal lifespan of RBC
110-120 days (4 months)
symptoms of anemia:
dyspnea at rest, fatigue, lethargy, confusion, CHF, angina, MI, and arrhythmia, and depend on both MAGNITUDE and the RATE OF DEVELOPMENT
in acute bleeding, what is the main problem?
hypovolemia
normal adult blood volume
~5L
blood volume according to age:
adult female: 65mL/kg
adult male: 70mL/kg
children: 80mL/kg
neonates: 100mL/kg
when does shock happen and what are the symptoms?
when supply cannot meet demand. symptoms; confusion, dyspnea, diaphoresis, frank hypotension leading to permanent organ damage and possibly death
CBC:
H/H and red cell indices: MCV, MCH, MCHC, and RDW
reticulocyte count:
should be high if marrow is intact and responsive; if low look for problems in the marrow that impact cell production
WBC:
If low, consider bone marrow suppression; if high, consider infection, chronic inflammation or malignancy. Check for hypersegmented PMN’s whenever RBCs are macrocytic and reduced in number.
platelets
- If low, consider bone marrow suppression, hypersplenism, alcoholism, autoimmune states;
- If high, consider iron deficiency, inflammation, infection, malignancy, stress
microcytic anemia:
MCV <80fL
iron deficiency, chronic blood loss, alpha or beta thalassemia minor, and anemia of chronic disease/inflammation; lead poisoning
macrocytic anemia
MCV >100fL
B12, folate deficiency, alcohol abuse, Down syndrome, hypothyroidism, liver disease; also drugs (hydroxyurea, AZT), myelodysplasia, leukemia, reticulocytosis
Normocytic anemia
Acute blood loss, early iron deficiency, anemia of chronic disease, bone marrow suppression, chronic renal insufficiency, hypothyroidism, aplastic anemia, sickle cell anemia
iron deficiency anemia causes what most commonly
microcytic-hypochromic anemia
usual suspects of iron deficiency anemia:
NSAID use, gastric ulcers, heavy menses, colon cancers, blood donation; low dietary intake in pregnant women and children
an enzyme ______, on the brush border of the ________ and ________ reduces iron from ferric to ferrous making it more absorbable
- ferric reductase
- duodenum and proximal jejunum
most of the iron in the body is found where
hemoglobin
where are smaller percentages of iron found?
ferritin and hemosiderin
very small amount (3 mg) is present in the transport form which is?
attached to transferrin
iron is transported bound to a molecule called
transferrin
what measures transferrin levels
total iron-binding capacity (TIBC)
what is the main storage form of iron?
ferritin
labile form of iron storage
ferritin
stable form of iron storage which consists of ferritin and cell debris
hemosiderin
diagnostic test for iron deficiency
ferritin
indirect marker of the total amount of iron stored in the body
plasma ferritin- diagnostic test for iron deficiency
are platelets an acute phase reactant
yes
treatments for iron deficiency
- 325 mg ferrous sulfate po tid x 6 months w/ Vit C
- Ferrous gluconate 240/324 mg might be better tolerated
lead interferes with the biosynthesis of what?
heme
desire to eat non-nutritive things
pica
ingestion of lead
plumbophagia
compulsive consumption of ice
pagophagia
most common form of adult anemia
anemia of chronic disease
what are reduced during anemia of chronic disease
serum ion and transferrin saturation
Cytokines released in inflammatory and infectious disorders induce excess synthesis of what?
hepcidin
what is the primary intrinsic regulator of anemia of chronic disease
hepcidin
hepcidin, through the down-regulation of what it inhibits transfer of stored intracellular iron back into plasma, thereby blocking reuse of iron by the marrow
ferroportin, a transfer protein
levels of transferrin in fe def.
elevated
levels of TIBC in fe def
elevated
levels of ferritin in fe def
low
levels of transferrin in anemia of chronic illness
low
levels of TIBC in anemia of chronic illness
low
levels of ferritin in anemia of chronic illness
increased
structural abnormalities in the globin
hemoglobinopathies (qualitative)
underproduction of normal globin subunits
thalassemias (quantitative)
Caused by a genetic defect that results in abnormal structure of one of the globin chains of the hemoglobin molecule
hemoglobintopathy
what kind of traits are hemoglobinopathies inherited as
autosomal co-dominant traits
sickle cell disease is what?
autosomal recessive disease that leads to hemolytic anemia
sickle cell mutation
HbS
when do sickle cell symptoms begin
when HbF production ends
what creates painful crises lasting hours to days exacerbated by dehydration, acidosis, hypoxemia
vascular occlusions
salmonella osteomyelitis
if you get some salmonella in your GI tract you may not get sick but if it ends up in your bones and you have sickle cell- you are more likely to get infected and get sick. These only happens when you auto splenectomies your spleen.
what kind of cells will you see in a sickle cell disease smear?
normochromic RBC’s, nucleated RBC, sickle cells, Howell-Jolly Bodies, Retic count increased, increased bilirubin
short term sickle cell treatment
pain control, IVF in acute crisis (medically lowering the hematocrit and making the blood more viscous), oxygen
long term sickle cell treatment
transfusion red cell exchange aphaeresis hydroxyurea (promotes HbF production) PCN prophylaxis- prophylax with penicillin pneumoccal vaccination folate supplementation avodiance of smoking iron chelators
thalassemias
hereditary microcytic aenmia; unresponsive to Fe
Alpha-Thalassemia in what type of ancestry
asian
Beta-Thalassemia in what type of ancestry
mediterranean
Due to a deletion or mutation in one or more of the four alpha globin gene copies.
Alpha thalassemia
microcytic, hypochromic anemia with low MCV.
Alpha Thalassemia Trait
what can HbH disease cause?
moderate to severe anemia and splenomegaly
Hydrops fetalis (fetal congestive heart failure) = Bart’s Anemia
barts anemia
hydrops fetalis
congestive heart failure (fetal) swollen appearance of the patient.
what is beta thalassemia caused by?
polymorphic mutations in one or both of 2 beta globin (HB ß) genes
Beta Thalassemia Trait (Thalassemia Minor)
one normal gene and one with a mutation; hypochromic, microcytic; unresponsive to iron
Beta Thalassemia Intermedia
two abnormal genes but still producing beta globin unit variety(ies) with some functionality; the severity of the anemia and health problems experienced depend on the mutations
Beta Thalassemia major (Cooley’s anemia)
two (very) abnormal genes; no beta globin produced; no Hgb A
when does cooleys anemia appear
in an infant after 3 months of age after loss of Hgb F; life threatening anemia
atypical, abnormal nucleated erythroblasts with granules of iron accumulated in perinuclear mitochondria
sideroblasts
Sideroblastic Anemia
The body has iron available but cannot incorporate it into hemoglobin = ineffective erythropoiesis
causes of sideroblastic anemia
B6 (pyridoxine) deficiency Hereditary; isoniazid INH use Lead Poisoning Zinc Poisoning
Mnemonic for Microcytic Anemia
T- thalassemia A- anemia of chronic disease/inflammation I- iron deficiency L- lead poisoning S- sideroblastic anemia
bound in the duodenum to intrinsic factor, which is produced by gastric parietal cells of the stomach. The complex is then absorbed in the terminal ileum (receptors that can bind to the intrinsic complex B12) and stored in the liver
vitamin b12
inadequate b12 levels are due to what?
dietary deficiency or deficient absorption
deficient b12 absorption is found in what?
crohns disease short bowel syndrome cystic fibrosis bacterial overgrowth syndrome pernicious anemia
type of b12 deficiency caused by lack of intrinsic factor
pernicious anemia
what causes the lack of intrinsic factor
- atrophic gastritis- achlorhydria: destruction of gastric parietal cells
- anti- intrinsic factor antibodies
- gastric bypass
- gastrectomy
water without chloride. your stomach doesn’t make enough stomach acid
Achlorhydria
most important system to absorb B12
intrinsic factor
more sensitive method of screening for B12deficiency is measurement? why?
serum methylmalonic acid and homocysteinem levels. because they are increased early in b12 deficiency
what else is elevated in B12 deficiency
MMA and homocysteine
what is elevated in both b12 and folate deficiency
homocysteine
what are hypersegmented PMNs
white cell changes
if you give both a homocysteine test and MMA and only MMA is high, what is the deficiency?
folic acid problem
if you give both a homocysteine test and MMA and both are high, what is the deficiency?
B12 deficiency
neurologic problems
b12 deficiency
important to the formation of fetus brain
folic acid deficiency
Paresthesias- numbness or tingling
b12 deficiency
Big cells in the bone marrow
megaloblastic anemia
Big cells that get into the blood stream
macrocytic
causes of folate deficiency anemia
poor intake, pregnancy, ETOH, MTX
hypersegmented PMNs
folate deficiency anemia
what kind of cells can you see in folate deficiency anemia
howell-jolly bodies
where are megaloblasts found?
RBC precursors found in the bone marrow
where are macroctyes found?
in the peripheral blood stream
megaloblastic-macrocytosis can be caused by?
Folate and B12 deficiency
Intrinsic hemolytic anemia
hemoglobinopathies, some thalassemias, spherocytosis (osmotic fragility test), elliptocytosis, paroxysmal nocturnal hemoglobinuria, sickle cell disease; G6PD deficiency
Extrinsic hemolytic anemia
autoimmune, drug induced, HUS (hemolytic uremic syndrome), DIC (disseminated intravascular coagulopathy), metallic heart valves, infection, burns, hypotonic hemodilution
signs of hemolytic anemia
decreased haptoglobin
inclusions of denatured hemoglobin in the RBC found in G6PD deficiency
heinz bodies
bone marrow disorder where excessive RBC’s are produced (polycythemia rubra vera)
polycythemia
due to chronic hypoxemia (COPD), living at high altitudes
polycythemia
what can polycythemia lead to?
hyper viscosity
Normal MMA with elevated homocysteine suggests anemia secondary to?
pure folate deficiency
Low serum iron, elevated TIBC suggest?
iron deficiency
control of blood loss
hemostasis
first step in all wound healing
hemostasis
what does hemostasis do?
limits blood loss by precisely regulated interactions between components of the blood vessel wall, platelets, and plasma proteins
which natural set of anticoagulants keep hemostasis in check?
plasmin system and proteins C, S, and Z
what can unregulated activation of hemostasis cause?
thrombosis and embolism
what are the 3 major steps in hemostasis?
- vasoconstriction
- temporary blockage of break in the wall of a blood vessel by a platelet plug vis platelet adhesion
- formation of a fibrin clot
what happens during vasoconstriction during hemostasis?
the blood vessel will automatically contract to stop blood loss. Nervous system tells muscular wall to contract in order to slow the bleeding.
what happens during temporary blockage of a break in the wall of a blood vessel?
Platelets will start getting sticky and they will aggregate and adhere to one another to make a platelet plug. They don’t stay here for long but they are fast.
what happens during formation of a fibrin clot?
Fibrin is a plasma protein and a final step in the activation of a clotting cascade. There are 13-14 clotting factors. Fibrin is like a fiber that criss crosses and form a mesh in every direction. First it is loose then the clot matures and the mesh tightens and it forms a solid plug.
In the normal state, the endothelial cells of intact vessels prevent blood clotting with a heparin-like molecule called?
thrombomodulin
what does thrombomodulin do?
inhibits thrombin (clotting factor IIa)
When endothelial injury occurs, the endothelial cells slow secretion of thrombomodulin and increase secretion of what?
von Willebrand factor
what does von Willebrand factor initiate?
platelet adhesion
Factor II
prothrombin
Activated factor II
thrombin
primary hemostasis
platelet plug
secondary hemostasis
plasma coagulation system that results in fibrin mesh formation—starts within 20 sec of injury. Makes a better clot. Step 3.
Thrombocytosis (aka thrombocythemia)
too many platelets. excessive clotting or bleeding.
Thrombocytopenia
Not enough platelets- can only result in bleeding
Von Willebrand’s disease
(defective adhesion; not really the platelets’ fault)
you have some sort of defect adhesion of the platelets but the platelets are too many or too few, its that the factor is not there or doing its job so it doesn’t make the platelets sticky like it should. The lack of or abnormality of the Von Willebrand adhesion.
Tiny, microscopic bleeding capillaries that form spots. Enough in the skin take a lot of the surface of the skin. Can form little purple spots known as purpura. Purpura can form bigger patches known as ecchymosis- black and blue
Petechiae, some purpura
bleeding time and platelet count
Abnormal platelet count or the bleeding test will have an abnormality. Not great tests available for platelet function but for the count we do.
Local measures generally suffice to control bleeding
Putting pressure on the bleed
Thrombocytosis
Platelet count above 500k/microliter. 100,000-450,000 is normal count.
what can cause thrombocytosis/thrombocypenia?
Can be caused by an acute reactive process (an APR: recent surgery, bacterial infection, iron deficiency, or trauma) or a bone marrow disorder which is a malignancy known as essential thrombocythemia)- cancer on platelets or megakaryocytes
treatment for thrombocytosis/thrombocypenia
- Treat underlying cause if possible (is it an acute phase reactant?)
- Antiplatelet medications, unless there is bleeding (next slide)
- Platelet-pheresis might be needed. Blood is removed from the pt. platelets are removed then blood is given back to the patient.
- hydroxyurea or anagrelide to lower platelet count in high-risk patients two drugs used to lower platelet count
irreversibly blocks the aggregation of platelets by interfering with the production of. Thromboxane (causes vasoconstriction) (prostaglandin- involved in fever, vasomotor tone)
aspirin
P2Y12 inhibitors (ADP receptor blockade)
block platelet aggregation
Thrombocytopenia
- decreased bone marrow production
- increased splenic sequestration: spleen isn’t allowing them to go into circulation
- accelerated destruction of platelets (ITP, TTP): increased destruction
Idiopathic Thrombocytopenic Purpura (acute)
immune mediated ITP is mostly seen in children with sudden onset of severe thrombocytopenia following recovery from a viral illness.
Idiopathic Thrombocytopenic Purpura (chronic)
mostly seen in adults. the antibodies never go away and keep attacking your platelets
Thrombotic Thrombocytopenic Purpura (TTP)
Initiated by vessel wall injury initiating an exaggerated clotting cascade leading to a tetrad of thrombocytopenia, hemolysis (red cells), renal failure, and CNS signs (central nervous system problems- mild to severe) such as fluctuations in levels of consciousness, confusion, and seizures
The only major clotting factor not made by the liver.
Von Willebrand Factor
what does the von willebrand factor bind to and protect?
inactive factor VIII from spontaneous degradation
what is responsible for the uncoupling of factor VIII from vWF
thrombin
what makes platelets sticky?
Free vWF
shearing stress
when the blood is rapidly flowing
treatment for von willebrands disease?
- vWF/factor VIII concentrate
- recombinantvon Willebrandfactor (r-vWF)
- desmopressin, which raises vWF. Given for surgery, major trauma, or other active bleeding.
primary site of synthesis of most of the clotting factors as well as the proteins involved in the fibrinolytic (keeps coagulation factor in check) system.
liver
body’s natural system
of anticoagulation that serves as a constant servo-
mechanism offsetting the coagulation cascade
The fibrinolytic system
liver pro-coagulation factors?
vitamin K-dependent: II (prothrombin), VII, IX, X (2,7,9,10)
non-vitamin K-dependent: I (fibrinogen), V, XIII (1, 5, 13) basically all the other ones
liver anti-coagulation factors?
vitamin K-dependent:
proteins C, S, Z: made by the liver that interfere with the clotting cascade (not enough Vitamin-K)
non-vitamin K-dependent:
antithrombin-III and plasminogen
not synthesized by the liver and not vitamin K dependent
von willebrand factor (pro-coagulant)- vascular endothelial cells
thrombomodulin (anti-coagulant)
tPA (tissue plasminogen activator)- subendothelial tissue
important cofactor along many points in the coagulation cascade
Calcium (factor IV)
what are vitamin K dependent factors?
factors II, VII, IX, X, protein S, protein C, and protein Z
what do you see in coagulation factor disorders?
large palpable ecchymoses and large, spreading, deep soft tissue hematomas
what makes the fibrin clot tighten up?
factor XII
Prothrombin time (PT)
Tests extrinsic pathway and final common pathway
Activated Partial Thromboplastin time (aPTT)
Tests intrinsic pathway and final common pathway.
Thrombin time
tests for quantitative (fibrinogen deficiency) or qualitative (dysfunctional fibrinogen) defect. Thrombin is added to the patient’s plasma in the lab. Time till clot formation begins is noted. Measure of how long it takes for fibrinogen to make a cross link clot. Measures from after Fibrinogen (factor I) and down to where the clot is formed
What is the most common inherited plasma coagulopathy?
Factor VIII Deficiency: Hemophilia A
what does factor VIII deficiency cause?
hemophilia A
what is a common cellular coagulopathy?
Van B Disease
what does factor IX deficiency cause?
hemophilia B
second most common inherited plasma coagulopathy
hemophilia B
what is factor XI deficiency?
autosomal recessive. less severe form of hemophilia.
body’s natural system of anti-coagulation that keeps coagulation in check
plasmin system
what is plasmin?
proteolytic enzyme that lyses fibrin clots
what does protein S do?
activates protein C with the help of thrombomodulin
what does protein C do?
inactivates factors Va and Vllla
what does protein Z do?
inactivates Xa
what does antithrombin do?
inactivates thrombin (IIa) and Xa
what does thrombodulin do?
converts thrombin (IIa) into an anti-coagulant; helps protein S activate protein C
what does tissue factor pathway inhibitor (TFPI) do?
inactivates VIIa
what does warfarin do?
blocks the activity of Vitamin K
what is used to monitor the anticoagulant effects of warfarin?
Prothrombin time
naturally occurring mixture of varied chain lengths of glycosaminoglycans (GAGs) derived from porcine intestine
heparin
what does heparin activate?
antithrombin
what does antithrombin inactivate?
factor Xa and also inactivates activated thrombin
Warfarin messes with?
Vitamin K (2,7,9,10)- if you get a drug that messes with Vitamin K, it messes with everything Vitamin K is needed for. Messes with both coagulant factors and anti.
what does heparin bind to?
platelet factor 4 (PF4) which triggers the formation of anti-heparin antibodies
