Hemostasis Flashcards
Process of Hemostasis
- Start with vasospasm which causes vasoconstriction at the site of injury
- Von Willibrands factor is released which helps by binding to platelet receptors causing platelets to stick to the expressed collagen . vWF allows platelets to stick to the site of injury. Intrinsic pathway is activated by factor XII; extrinsic pathway is activated by tissue factors. These pathways lead to activation of factor X
- Need platelets to form the fibrin matrix and stick everything together. Prothrombin is converted to thrombin which is converted into fibrinogen which forms an insoluble fibrin thread around the platelets to hold it all together. In the clot itself, RBCs and neutrophils get trapped in which form a nice clot within the vessel
- t-PA is released when the process of hemostasis happens. If the clotting cascade were to start and nothing ever stopped it, the result would be massive clotting throughout the entire body. The fibrinolysis starts around the time the body is making the clot so that it breaks it down to prevent it from getting too big
The blood clotting cascade
The extrinsic pathway starts the clotting process with some type of trauma causing constriction which causes tissue factor to release in the form of a plug
The intrinsic pathway is starting with platelet aggregation itself. The platelets get called to vWF to begin sticking together.
Where meds are affected in the process: thrombin inhibitors (heparin, etc.) act in the extrinsic pathway (decrease the formation of the platelet plug), act at platelet aggregation (not calling as many platelets together and they aren’t sticking together), affecting thrombin and factor XII. Heparin acts in a lot of different places which makes it most effective. Aspirin platelet inhibitors only affect the ability of platelets to stick together. Vitamin-K dependent meds (Warfain, etc.) affect the conversion of prothrombin to thrombin. Tissue plasminogen activator (t-PA) interferes with the fibrin clot by introducing plasmin to assist with clot lysis.
Calcium role: low calcium levels= more inclined to bleeding
Clotting deficiencies: hemophilia is factor VII. Factor IXa needs factor VII to covert. We are halfway down the cascade is there is a Factor VII deficiency
Process of fibrinolysis
Plasminogen is released
Plasminogen activators and thrombin digest the fibrin clot into the fibrin degradation products
Lab- fibrin split products: the more clot that’s breaking down, the more split products there will be
Platelet labs
140-400,000
Lasts 7-10 days
Important when looking at effectiveness of platelet inhibitors (e.g., aspirin which lasts 7-10 days)
The platelets made under the effects of aspirin will have the same effect as the lifetime of the platelet
Bleeding time
3-10 minutes
Not typically done anymore
A cut is made on the forehead or earlobe and time it takes to clot without pressure is measured
Thrombin time
7-12 seconds
The time needed for blood to clot when thrombin is added
Fibrinogen defects, DIC (disseminated intravascular coagulation), streptokinase therapy are the reasons to measure this. Thrombin times need to be sent on ice because want to prevent them from clotting
PTT (aPTT)
21-35 seconds
Activated PTT (aPTT) is more sensitive to monitor Heparin; otherwise they are the same. If patient is on Heparin, their levels should be 1.5-2x the normal (want them higher). Anything greater than 70 seconds, the patient is at risk for spontaneous bleeding
Low levels of PTT occur after hemorrhages and very early in DIC- looking at using up those coagulation factors
PTT shows us a defect in intrinsic thromboplastin system and extrinsic coagulation mechanisms
PT
11-13 seconds
Measures a defect in the extrinsic system. Directly affected by Vitamin K levels and are decreased in alcohol abuse. Alcohol abusers are at an increased risk for bleeding because of the extrinsic pathway
PT & PTT are looking at normal within the same lab. INR looks across international standards. This is why INR is looked at more often that PT and PTT
INR (international normalized ratio)
0.7-1.8
For someone on Warfarin, levels will be 2-3x the normal for effective coagulation
Plasminogen
Males: 76-124% normal or 0.76-1.24 fraction
Females: 65-153%
Infants: 27-59%
In a normal clot, plasminogen is absorbed in the clot, turns to plasmin which gradually dissolved the clot. It’s the dissolving part of the clot. Antiplasmin in the plasma deactivates the plasmin. When abnormal clotting occurs, excessive plasmin is present in the plasma and antiplasmin is depleted causing bleeding. The more plasminogen we have, the higher our risk for clotting is
D-dimer
<250 ug/l or <1.37 nmol/l
Not a common lab; will be drawn in patients with pulmonary embolisms and confirming diagnosis of DIC
It confirms that thrombin and plasmin have been made
Fibrinogen
200-400 mg/dl
The enzyme action needed to convert fibrin (part of the normal clot)
Increased in tissue damage and inflammation
A patient is transitioning from IV Heparin therapy to oral Warfarin. Therapeutic anticoagulation of the patient is best assessed by:
A- partial thromboplastin time of 24.3 seconds
B- Prothrombin time of 18 seconds
C- INR of 2.5
D- bleeding time of 5 minutes
C
INR is more accurate because of variations that occur with PT values across different labs. The goal of warfarin is to maintain INR between 2.0-3.0 regardless of the actual PT in seconds
Assessment
History: chronic diseases (GERD, ulcers, Chrons, etc.), meds (aspirin, Coumadin, etc.), is the problem r/t bleeding or anemia (anemia’s can be caused by bleeding)
Diet- great consumption of alcohol decreased clotting factors, high in Vit K (e.g., green leafy vegetables) increases clotting, low calcium decreases clotting
Skin- pallor, cyanosis (extreme bleeding or anemia can cause decreased oxygenation), do their gums bleed after brushing teeth, petechiae (pinpoint red dots that do not Blanche when pushed on), ecchymosis (bruising)
HEENT- nosebleeds or epistaxis
Respiratory- dyspnea and fatigue may be a possible pulmonary embolism
Cardiac- history of MI, pulmonary embolism, A-fib (or other cardiac dyrhythmias) may increase the risk for clot
Abdomen- GI assessment
MS- calf measurements (if one is bigger than the other, a clot is suspected), positive Homens sign (pain with dorsiflexion of the foot)- negative sign does not mean there is not a clot
Renal- hematuria, history of chronic diseases with anemia’s
Hemophilia
X-linked recessive- all X’s must be affected; boys are more at risk
Deficiency of Factor VIII or IX necessary for formation of thromboplastin
Hemophilia A: factor VIII disorder
Hemophilia B: Factor IX disorder
Bleeding into the joint spaces are most common because they have the most stress on them with daily activities: nosebleeds, knee bleeds; kids may need to be hospitalized to have their knees drained
Have a humidifier on furnace to help prevent nosebleeds
If they bleed, apply pressure and elevate until can give them whatever Factor they are missing via IV. Teach parents how to start peripheral IVs and give Factor at home. Teach them to reconstitute with normal saline and pull IV out after factor is given
DDAVP (Demopressin) to help concentrate clotting factors
Prevent bleeding: no contact sports; encourage activities that are not stressful on joints and things that will not increase risk for bleeding, bruising, or head injuries
Von Willebrand Disease
Autosomal inherited
Risk is equal in male and females
Control bleeding and replace missing factors
DDAVP (Desmopressin) to help concentrate. Typically do not give vWF as injections
vWF sticks the platelets to the site of bleeding. Typically not as bad as in Hemophilia. They can have joint bleeds, nose bleeds, etc.
Ice packs for minor cuts or bruises. Typically do not need to do anything.
Often not diagnosed in women until first menses where the bleeding does not stop. vWF will be drawn and labs will be lower in these patients. Some aren’t diagnosed until they get pregnant and have a postpartum hemorrhage
Immune Thrombocytopenia Purpura (ITP)
Platelet count less than 150
Acute or chronic
Autoantibody destruction of the platelets
Steroids, IVIG
Not genetic
Example: child has normal flu/cold, small fever, feels crummy, 5 days later, they feel great, up and running around. Petechiae are noticed. Scratching causes petechiae in the skin to form due to capillary bleeds
Immune system kicks into overdrive during flu/cold and begins to destroy platelets. This makes them high risk for bleeding.
Give immune factors (IVIG, IV immunoglobulins) which is an artificial immune system that stops the body from needing to produce its own. If we stop producing our own, we stop destroying the platelets and eventually normalizes. Also may be started on a course of steroids until platelets come back up.
For most kids, platelets begin to rise, immune system normalizes, and problems go away after 5 days. There are a small amount of kids that will end up with chronic ITP
Chronic ITP
Normal platelets of 50-100
Bleeding risk is very high. No contact sports
If less than 50, may need periodic IVIG injections or infusions. Girls may need to be put on Depo-Provera shots to prevent menses
Can become very anemic from losing blood
If we have autoantibody destruction of the platelets, they will not get a platelet bump from infusing platelets. Platelet infusions do not work. Someone with acute bleeding like a subdermal hematoma, platelets will be helpful. Platelet infusions themselves do not work with ITP because they are automatically destroyed
Supportive care and bleeding prevention until able to raise platelet counts go back up. Kids with chronic ITP may need to wear a helmet (r/t falling down a lot) to prevent any injuries
Regularly monitor platelets to see if need IVIG
Splenectomy may be done to cause less platelet destruction.
Post-op complications: very high risk of bleeding due to removal of a highly vascular organ
Bleeding disorders in women
Von Willebrand Disease (vWD): most common bleeding disorder in women; effects 1-2% of the general population; if the patient has menorrhagia, incidence of vWD is 20-25%
Menorrhagia can lead to chronic pain, anemia, hospitalizations, blood transfusions, limitations in activities,
Symptomatic carriers of hemophilia: mucotaneous- nose bleeding, mouth bleeding, easy bruising; 2 categories: inherited a gene from father and mother; or she is a genotype carrier who has experienced extreme lyonization of the hemophilia gene causing factor VIII or IX to be turned off . Lyonization is X-inactivation where one copy of the X chromosome in each female cell is inactivated to prevent female cells from having twice as many gene products from the X chromosomes as males
Rare bleeding disorders in women: factor XI deficiency (very rare; autosomal inheritance pattern-males and females equally affected); common in Jewish, European, eastern, Israeli heritages
