1. Large molecule
2. Sticks to platelets and subendothelial cell
3. Changes the shape of platelets
4. Conformational change at GP 2b/3a receptor (asa site)
5. carries factor 8

1. not cells, fragments 
2. Fx. latch to vessel wall, activate
3. produce thromboxane A2
4. Live 7-10 days
5. 33% are in the spleen
6. production is regulated by thrombopoetin 
7. Membrane contains glycoprotein 2b/3a,                                   phospholipids (coagulation binding sites)       absorbed coagulation factors
8. Has granuales w/ hemostasis mediatiors, vasoconstrictors and platelet derived growth factors

1. Produced in  megakarocytes of the liver, kidney, muscle, and bone marrow
2. regulates platelets

1. after binding to college, platelets become activate
2. this stabalizes platelet-platelet matrix
3. releases thromboxane A2 to get more platelets
4. releases serotonin, histamine to make smaller arteries
5. localizes fibrin formation
6. accelerates fibrin formation
7. protects clot from being broken down (fibrinoglysis)

1. Extrinsic (tissue extracts)
2. measures how long it takes blood to clot. 
3. Blood exposed to tissue extracts
4. check whether medicine to prevent blood clots is working
5. may also be called an INR test
6.  Prothrombin time is an important test because it checks to see if five different blood clotting factors (factors I, II, V, VII, and X) are present. 
7. An abnormal prothrombin time is often caused by liver disease or injury or by treatment with blood thinners.
8. 
   

1. Intrinsic (blood exposed to collagen from vessle injury)
2. may be used to find out if the right dose of heparin is being used.
3. The activated partial thromboplastin time (APTT) test is used after you take blood-thinners to see if the right dose of medicine is being used

blocks luptake of vitamin K in liver

blocks factor 2, 7, 9, 10

1. From green leafy vegetables, fish, liver, meat, eggs, and cereals (contain smaller amounts)
2.         Vitamin K is also made by the bacteria that line the gastrointestinal tract.
3. without vitamin K your blood wound not clot. 
4. factors 2, 7, 9, 10

1. Blood vessel breaks

2. Blood vessel spasms (1min)

3. von Willebrand's makes a platelet plug

4. Collage is strung from the platelets to the subendothelial matrix (fish net)

5. Plates activate, creating phospholipid platform 

6. Coagulation cascade initiates on plateform

7. 2b/3b receptors bind platelets together

8. Platelets (degranulated) release ADP and thromobane 

9. Tissue factor activates tissue coagulation cascade

10. Insoluble fibrin (supports clot)

11. This seals away factors

12. Clot process stops

13. Trapped platelets retact, clot shrinks

1. links platelets together 
2. located on platelets
3. Glycoprotein IIb/IIIa inhibitors can be used to prevent blood clots in an effort to decrease the risk of heart attack or stroke.
4. It is a receptor for fibrinogenand aids in platelet activation. 

1. tissue plasminogen activator (t-PA)
2. (protease  found on endothelial cells), catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for clot breakdown. converts plasmin dissolves fibrin strands
3. Protein C and S inhibit clotting factor 5

1. Anti-thrombin 3
2. Protein C
3. Protein S                                                                                               mneumonic: My 3 c.at.s scratch clots.

serum levels of fibrin

D-dimer

fibrin split products

These can help you detemine if 

Inhibits cyclooxygenase 1 (COX1) forever!

Thromboxane can never be produced by platelets (lonely)

1. mediator of pain and inflammation.
2. expressed on leukocytes and mature platelets (platelet neutral)
3. decrease production of anti-thrombogenic prostacylin
4. leads to strokes, HTN and MI

reversibly bind to COX-1

can compete with ASA

1. inhibits platelet COX-1 and Cox 2 (irreversably) enzyme from producing thromboxanne TxA2
2. Stop asparin before surgery 7 - 10 days prior, use heparin (short acting) as a bridge treatment
3. Asparin competes with NSAIDs
4. Increases PT time

Inhibits platelet COX-1 (reversable) and Cox-2

Concentration dependent inhibit COX-1

 good for platelet/arterial problems

venous needs

Lepirudin Refludan (discontinued)

argatroban, i.v.

dabigatran (prodaxa) (oral) (No blood tests) not reversible, c.i. renal faluire

does not affect platelets as much 

Heparin (i.v.)

Low molecular weight heparin (renal cleared)

Heparin analog (fondaparinux)  

1. inhibits factor 10 
2. inactivates thrombin via anti-thrombin 3
3. no thrombin
4. prevent clot from extending 
5. heparin iv is good for kidney problems
6. clears in 12 hr

1st: ASA

2nd: Plavix

Thrombin generation time is essential 

Prodaxin (dabigatran, direct thrombin inhibitor)

coumadin (takes 48hrs to work, use hep short term)

1. Occur in muscles 
2. Solid organs
3. Joints, (arthritus)                                                        

1. Platelet count
2. morphology

measures vitamin K dependent coagulation factors (2, 7, 9, 10) 

extrinsic and intrinsic

not routine

cell morphology

invasive test

bone marrow aspirated from hip

1. Blood vessel dissorders
2. thromocytopenia or abnormal platelet function
3. low levels of mult. factors or vit k
4. low levels of specific factor 
5. Consumptiv coagulation (DIC)
6. Circulating inhibitors of factors

1. Influmation: Vasculitis (symptom)
3. Structure: senile, steroids, scurvy, defects in cellular wall (Ehlers danlos syndrom) purpura
4. Steroid induced purpura
5. Scurvy
6. Viral infection (Hep, EBV, HIV)
7. Drugs
8. Connective tissue disease (Systemic lupus erythematosus)

1. Decreased production (meds, bone marrow, nutrition)
2. Increased breakdown. 
3. Increased storage.

Normal values 150K to 400K

panic at <30 and >500K

1) Medications can damaging megakaryocytes 

(Thiazide diuretics, alcohol, estrogen, decreased B12

folate deficiency)

2) Bone marrow diseases: Leukemia, BC, lymphoma, 

3) Myeldysplasia ineffective production (or dysplasia) of the myeloid class of blood cellsand myelofibrosis  (marrow is replaced by scar)

4) Congentital diseases

1.) Splenomegaly -> increased trapping ->50-100K

caused by liver dz, leukemia, spleen malignant

1) Immune mediated: auto-antibody coated platelets, cleared by spleen (severe thrombo

2) non-immune: consumption of platelets 

1.  Immune thrombocytopenic purpura (ITP)

2. Thrombotic thrombocytopenic purpura

3. Hemolytic-Uremic syndrom (HUS)

4. Heparin-induced thrombocytopenia

5. von WIllebrand diseases

6. Uremia (high level of nitrogen waste products in the blood).

1-6 yr old boys, more common in children

30-40 females

uncommon in people over 60 - > myelodysplastic

1. viruses that cause chicken pox, hepatitis C, and AIDS, can prompt antibodies that cross-react with platelets. 
2. Gastroenteritis

1. Medications,
2. diseases (lupus, leukemia
3. HIV
4. myelodysplastic diseases 
5. weight loss
6. night sweat
7. splenomegaly

1st: Steroids

2nd: Intravenous Immunoglobin

3rd: splenectomy

1. Do not look systemically ill!
2. sudden onset (children)! slow for adults
3. (petechial rash)
4. focal or local neurological deficits
5. fundiscopic exam reveals retinal hemorrhage
6. jugular vein distention
7. Abnormally heavy menstruation
8. Easy bruising (purpura)
9. Nosebleed or bleeding in the mouth
10. distal heart sounds
11. abdominal pain

1. (CBC) shows a low number of platelets (severe).

1. Bleeding time is prolonged.

2.  (PTT and PT) are normal.

   periphreal smear: norm. RBC and WBC morph,

   big reticulated large platelets (immature)

3. Platelet associated antibodies may be detected. 

   A bone marrow aspiration or biopsy appears normal or may show a greater than normal number of cells called megakaryocytes.

1st:  d/c any causitive drugs and Prednisone (oral), solu-medrol (iv); avoid asparin, warfarin, and ibuprofen, refer to hemotologist (predinsone decreases autoantibody production and decreases sequestion)

 Splenectomy

filter antibodies

gama gobulin

new: thrombopoeitin receptor agonist

5% die

most respond to antibiotics

relapses are common

1. Classically :Quinidine (arhythmia), quinine (tonic water),
2. ABX: PCN, sulfa, cephalsporins, vanco)
3. ANti-hypertensive: thiazides, ace-inhibitors
4. Cimetidine (tagament) is used to treat ulcers; gastroesophageal reflux disease (GERD), 

Heparin induced has the potential to form clots (catastrophic thrombotic complications)

1.  danaparoid (organin, inhibits factor 10),
2. lepirudin Refludan, discontinued
3. argatroban , fondaparinux  or bivalirudin, not unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) therapy or initiation/continuation of vitamin K antagonists

Surgical patients (cardopulmonary bipass)

patients given heparin for longer than 4 days

1. To link platelets with the subendothelial membrane of the injury site: Von Willebrand factor acts like glue to help the platelets stick together and form a blood clot.

2. To carry and stabilize Factor 8

Heredity

acquiring vWB disease is rare

Very common 1%

Symptoms are worse in women!

milder than hemophilia

life long excessive bleeding: menorrhagia, epistaxis (bloody nose)

easy to bruise, gingival bleeding

worse with ASA

GI bleeding is uncommon!

prolonged PTT (half the time)

PT is normal

low vWF levels

platelets can be normal!

1. avoid ASA
2. give DDAVP (desmopressin acetate) to stimulate von Willefactor.
3. factor 8 conc. with von Willefactor
4. Refer to hemotologist

1. Renal failure causes platelet dysfunction
2. nitrogen products build up
3. anything that reduces blood flow to kidneys inhibits filtration (
4. Burns
5. Conditions that allow fluid to escape from the bloodstream
6. Long-term vomiting, diarrhea, or bleeding
7. Loss of blood volume (such as with dehydration)
8. heart cannot pump enough blood or pumps blood at a low volume
9. Shock

• • Confusion

  • Decreased alertness

  • Decreased or no urine production

  • Dry mouth

  • Fast pulse

  • Fatigue

  • Pale skin color

  • Swelling

  • Thirst

  Other symptoms may include:

  • Excessive urination at night

  • Pain in the abdomen

• Collapsed neck veins

• Dry mucus membranes

• Little or no urine in the bladder

• Low blood pressure

• Low heart function or hypovolemia

• Poor skin turgor

• Rapid heart rate

• Reduced pulse pressure (difference between systolic blood pressure and diastolic blood pressure)

• Signs of acute kidney failure

The following tests may be done:

• Blood creatinine

• BUN

• Urine osmolality and specific gravity

• Urine tests to check sodium and creatinine levels and to monitor kidney function

Intravenous fluids, including blood or blood products, may be used to increase blood volume. After blood volume has been restored, medications may be used to increase blood pressure and heart output. These may include dopamine, dobutamine, and other heart medications. The cause of the decreased blood volume or blood pressure should be diagnosed and treated.

If the person has other symptoms of acute kidney failure, treatment for it should include:

• Dialysis, including hemodialysis or dialysis inside the body (peritoneal dialysis)

• Diet changes

• Medication

3 types:

X-linked deficiencies, mostly in males

factor 8 is most common

Hemophilia C is chromosome 4

66% have a family history

Replace factors, i.v.

encourage family to get screened. 

refer to hemophilia treatment center

*pt's can release atuoantibodies towards exogenous factors

Hemarthrosis (Synovial inflammation)

Hemarthroses leads to join damage

muscular hematomas

avoid asparin

Oozing bleading from everywhere

back and forth from forming a clot to oozing blood

uncontrol clotting followed by massive hemorrhaging

associated with gram negative infections

cancer

Cancers

transfusion reactions

burns 

pregnancy complications

endothelial damage

retained placenta

sepsis

bruising 

frank bleeding

peticheiae

low blood pressure

epitaxis

 oozing blood from orphases

over 500K

autonomous overproduction by megakaryocytes (more common

myelodysplastic/myeloproliferative disorder

cytokine driven reaction process:

reaction thrombocytosis (less common)

post operative status, malignancy, splenectomy, and iron deficiency anemia or blood loss

Ask about infections surgery or trauma, symptoms and infection, hx of Fe deficiency, mematologic disorder and s/s 

headache

bleeding

thrmobosis

atypical chest pain

lightheadedness

visual symptoms

numbness and tingling of fingers

repeat lab

peripheral smear

Serum ferritin

CRP

ESR (erythremacyte sedimentation

platelet apheresis

low dose of asa

NO (vasodilation), ADPase and prostacyclin (vasodilator)

are release from granules of platelets

 membrane receptor that initiates the extrinsic coagulation pathway (TP) 

Cells in the neighborhood around blood vessels have tissue factor on their surfaces, whereas cells inside the vessels do not.

2b/3a antagonist

prevent platelet aggregation

good for platelet problems

What 5 events happens when platelets activate?

1. Stablization of platelet to platelet

2. recruitment of additional platelets

3. Vasoconstriction

4. fibrin formation

5. Protection from fibrinolysis

i.v. facilitates Antithromin 3 (clot buster), which inactives thrombin and factor X

Low molecular weight (LMWH) inactivates factor X (subq)

The fancer the heparin the less thrombin involvement