heme

what is hematocrit? 

normal level?

RBCs and formed elements 

45% whole blood 

what is hemostasis

stoppage of blood flow - slowing and stopping bleeding when a vessel is injured 

prevents hemorrhage and loss of blood volume, defends against infection

what are the 3 main phases of hemostasis

vasoconstriction

platelet plug formation

coagulation (clot) 

what happens in vasoconstriction

temporarily closes vessels to limit blood loss

enhanced by tA2 (released by platelets) and endothelin-1

what are the common platelet plug inhibitors

COX-1 inhibirots (aspirin)

thienopyridines (clopidogrel, ticlopidine)

what are the 3 main stages of coagulation

activation pathways

thrombin formation

thrombin clot formation (mesh catches RBCs)

why is the extrinsic clotting pathway extrinsic?

activated after damage like a cut or wound

how fast does the extrinsic pathway cause clotting?

intrinsic?

15 seconds (faster)

1-6 minutes (slower, more steps)

factors involved in the extrinsic pathway 

7 → 3 → activate 10

factors involved in the intrinsic pathway

12 → 11 → 9 → 8 → activate 10

factors invoved in the common pathway

10 (stuart) → 5 → 2 (thrombin) → 1 (fibrin)

what happens in the terminal steps for both clotting pathways

activation of factor 10, conversion of prothrombin to thrombin

thrombine converts fibrinogen to fibrin

bleeding that occurs to the defects in the extrinsic system are more/less severe than defects in the intrinsic pathway?

less

what are the common anticoagulant drugs and what do they do?

warfarin: alters vitamin K

heparin: inactivates factor 10, suppress fibrin formation, block cascade

formation of both thrombin and fibrin requires what mineral 

calcium 

vitamin K deficiency is common in what population

newborns

-also not present in breastmilk - exclusively breastfed infants may be vK deficient

why do newborns have an increased risk of vitamin K deficiency

intestinal flora not yet established

poor placental transport - limited reserves

sterile intestines - no enteric microbial synthesis

limited hepatic synthesis of clotting factors

cells from what organ synthesize prothrombin, fibrinogen, and other plasma proteins

liver

how does the body get vitamin K

absorbed by small intestine from food OR synthesized by gut bacteria

why do patients with obstructive jaundice (blocked bile duct) require preoperative vitamin K

inadequate vitamin K can → deficient/low prothrombin → bleeding disorders

clot retraction occurs within __ minutes after clot has formed

20-60

platelets contain small amounts of ___ and ___.

___allows hemostasis and retraction

actin and myosin

contraction

when does clt dissolution happen? 

what happens? 

shortly after formation

reestablishes blood flow

what is fibrinolysis

clot dissolving

what is the prooenzyme for the fibrolytic process

plasminogen

what does plasminogen do

concerted to plasmin → plasmin digests fibrin strands of clot

what proteins can be used clinically to dissolve a clot

streptokinase (plasminogen activator)

streptococcus, staphylococcus, and e coli: release anticlotting agents 

what drug has been recognized for early treatment of strokes?

what happens if administered in 6 hours? 3?

tPA: tissue plasminogen actovator

within 6 hours - improve blood flow, greatly reduce serious after effects of stroke

within 3 hours - most patients recover by 3 months - some will demonstrate bleeding into brain (45% fatality)

normal platelet count

150,000-450,000/microL

what is thrombocytosis

elevated platelet count - may reach above 1,000,000/microL

how does thrombocytosis occur

stimulate thrombopoietin production → rapid megakaryocyte proliferation

what can cause (primary to) thrombocytosis 

myeloproliferative disorders (polycythemia vera, myelogenous leukemia) 

infecrion, cancer, surgert, inflammtion from crohns, RA 

what is polycythemia vera

upregulated RBCs

what do megakaryocytes do

break into platelets

what are the 2 pain inherited hypercoagulability disorders

factor 5 leiden mutation - increases clot formation → common pathway hyperactivity

antithrombin deficiency - lack clotting inhibition

what can lead to an acquired hypercoagulability disorder 

venous stasis, myocardial infarction, cancer, smoking, obesity, oral contraceptives 

what is VTE

venous thromboembolism, DVT

seen in those with malignant acquired hypercoagulability

¼ people with VTE will have occult malignancy. what does occult mean?

asymptomatic

petechiae (red dots, global vasodilation) and purpura (areas of bruising) are common signs of what

platelet deficiency

what is thrombocytopenia 

reduced platelet number 

what can cause thrombocytopenia

increased sequestration of platelets in spleen

malignancy causing impaired platelet production

decreased platelet survival in circulation

what drugs may cause DITP (drug induced thrombocytopenia)

aspirin, anticonvulsants, antivirals, antibiotics

why does DITP happen

initiate immune complex formation → antibodies destroy platelets

intermedate onset of DITP is attrbuted to

herparin and quinine

what drugs are associated with late onset DITP

antoconvulsants (carbamaxepine)

antibiotics (cefriaxone)

when does recovery in platelet count occur with DITP

rapidly upon discontinuation of drug - regardless of onset time

what happens when someone FIRST INITIATES heparin as an anticoagulant 

panicked response - increased risk for clotting bc immatue megakaryocytes release and activate MORE platelets to create solid clot-like mass

THEN there is a drop in platelet count 

__% people treated with heparin develop HIT (heparin induced thrombocytopenia)

10

HIT occurs within ___ days of heparin treatment

2-5 days

1-5% patients treated with heparin will experience a lief threatening ____ event within 1-2 weeks of the start of therapy

thromboembolic

how to detect HIT? 

why?

lab tests to detect serotonin release assay 

platelets release serotonin when activated → vasoconstriction

serotonin release detected to determine if heparin is causing activation of platelets and HIT

how to treat HIT

immediately discontinue heparin and initiate alternatie anticoagulation therapy

what is hemophilia A 

mutation of factor 8 gene 

90% cases produce too little factor 8, 10% produce defective form 

who gets hemophilia A

x linked RECESSIVE disorder - primarily males

differentiate between mild, moderate, and severe hemophilia A

mild: 6-30%, bleeding with trauma, undetected in childhood

moderate: 2-5%, bleeding with trauma, undetected in childhood

severe: 1%, bleeding at childhood/circumcision, spontaneous, 2-3x/month

clinical presentation of hemophilia A

bleeding in soft tissues (GI tract and weight bearing joints)

what joints are most affected in hemophilia A?

vessels?

hip, knee, elbow, ankle

circumflex and genicular bleeding inflames synovium → fibrosis and contractures

how to diagnose hemophilia A

blood tests reveal low factor 8

treatment for hemophilia A

prevent trauma, avoid NSAIDs

factor 8 replacement therapy (can be abortive or preventative) to treat or prevent bleeding and reduce msk damage

what coagulation factors are produced in the liver 

factors 5, 7, 9, 10, 11, 12, prothrombin, fibrinogen 

liver diseases may limit the synthesis of which clotting factors?

what is required for normal activity?

2, 7, 9, 10, prothrombin

vitamin K

vitamin K deficiency is very likely/unlikely

unlikely, unless intestinal synthesis/absorption is impaired

who is vitamin K deficiency most notable in

-newborns

-broad spectrum antibiotics that destroy flora

what is spectrin

network of fibrous proteins - allows flexibility in blood cell, allows it to squeeze into capillaries and into peripheral tissue

what is ankyrin

protein on inner surface of membrane attaches to spectrin and integral proteins on membrane

what is spherocytosis 

abnormality of spectrin and/or ankyrin 

what does a hemocytoblast do

makes every blood cell

what is a reticulocyte

immature RBC, looked at in a blood panel for anemia

reticulocytes should be ___% all RBCs.

what does it tell you if the measure is higher

10%

panicked response, releasing as much as possible

what is erythropoiesis 

RBC formation 

in the RBC chain, hemocytoblasts differentiate to become

proerythroblasts

what are the 2 lines that come from differentiation of a hemocytoblast?

where do they each occur?

myeloid: marrow

lymphoid: thymus, lymph nodes

what gets made from the myeloid line

RBCs, platelets, granulocytes

what is made from the lymphoid line

lymphocytes

how long does it take for a stem cell to mature into an RBC?

into a reticulocyte?

7 days

5 days

RBCs begin differentiating with the appearance of ___.

they become ___ after further differentiation.

these cells lose their nuclei to become ___,

eventually shredding their reticulum and becoming ___ over the next 1-2 days 

proerythroblasts

polychromatic erythroblasts

reticulocytes

mature erythrocytes 

what do polychromatic erythroblasts do 

produce hemoglobin 

what is the largest controller of erythropoiesis

tissue oxygen needs

what is commonly abused in endurance sports

EPO - naturally released by kidnets in times of low oxygen → develop reticulocytes and mature RBCs

what plays a major role in proper erythropoiesis

IGF-1

insulin like growth factor 1, basically GH

what cells in the kidney can detect oxygen content through chemoreception 

peritubular cells 

describe adult vs fetal hemoglobin

adult: 4 chains - 2 alpha, 2 beta

fetal: 4 chains - 2 alpha, 2 gamma

why is there a differentiation between adult and fetal hemoglobin

fetus has to outcompete mother for oxygen

what acts as a buffer between maternal and fetal blood

placenta

what is heme? 

globin? 

red pigment 

protein chain 

oxyhemoglobin vs carbaminohemoglobin

oxy: bound to 4 oxygen molecules

carbamino: bound to carbon dioxide

what chains are abnormal in sickle cell disease?

what is used to treat?

beta

fetal hemoglobin

normal hemoglobin levels 

13.5-17.5 g/dL

hemoglobin levels below ___ g/dL are considered candidates for transfusion

7

transfusions of whole blood or RBCs are used to treat ___

anemia

___antibodies attack/reject type B blood

B

what antibodies and antigens are found in type A blood 

antibodies: anti B 

antigens: A 

what antibodies and antigens are found in type B blood 

antibodies: anti A

antigen: B

what antibodies and antigens are found in type AB blood 

antibodies: none

antigen: A and B

what antibodies and antigens are found in type O blood 

antibodies: anti A and anti B

antigen: none

what is agglutination 

clumping 

agglutinins and immunoglobulins are other names for ___ dissolved in plasma that react with specific blood group antigens

antibodies

agglutinogens are another name for

antigens

plasma (always/never) contains antibodies against antigens present on its own RBCs

never

what does it mean to have Rh positive blood 

Rh or D antigen present on RBCs