Module 7 Part 1 - Hematology Flashcards
Sickle Cell Anemia (SCA)
a group of autosomal recessive disorders which manifests as an anemia with sickle or crescent shaped RBCs d/t presence of abnormal type of Hgb S
What sort of genetic inheritance pattern is SCA?
Autosomal Recessive
What is Hgb S associated with besides SCA?
Protection from cerebral malaria (common disease in Sub-Sahara Africa
What populations most frequently have SCA?
Frequency of the disease is high in Mediterranean and African Populations
30% of their populations have the trait (carrier or disease)
What is the rate for an African American carrying the SCA gene (Sickle Cell Trait) in the US? How many African American newborns have SCA?
1 in 12 (8%) carrier rate
1 in 500 have SCA
90000-100000 people with SCA exist in the US currently with 50-70% reaching ages 40-50 – so its not longer a death sentence
What is the only treatment with a chance to cure SCA?
Bone Marrow Transplant
What are some examples of Sickle Cell Disorders?
Sickle Cell Anemia
Sickle Cell Hgb C
Sickle Cell Beta Thalassemia Disease
Under what conditions does Hgb S Sickle?
- Vasodilation causing conditions: Low pH, high H+ concentration, Acid build up (acidosis)
- Low O2, High CO2
- Exercise
- Dehydration
- Infection (especially bacterial)
- Stress and Anxiety
- Fever
- Exposure to the cold and high altitudes
If a person has the SCA trait (is a carrier) how much of their Hgb will be Hgb S?
Heterozygous for the trait (Ss) = 40% is Hgb S
If a person has the SCA disease how much of their Hgb will be Hgb S?
Homozygous Recessive (ss) = 90% Hgb S and a greater chance for sickling
Can Hgb S return to its original shape?
Yes! with enough oxygenation it can
However, the more times it does this the less likely it is to return to shape on subsequent events
What kind of Hgb is high in newborns? What do we do if the newborn will have SCA?
Hgb F
Hgb F is all metabolized by 5-6 mo post-birth, so if they are homozygous recessive we give hydroxyurea to increase Hgb F production so it is not metabolized as quickly and delay the sickling further out
What will be the hereditary pattern for parents that are AA (no SCA trait) and SS (homozygous rec for the trait) be like for SCA?
100% chance of child being a carrier
0% chance of children having SCA or being non carriers
What will the hereditary pattern for parents that are AS and SS be like for SCA?
50% chance of child having SCA
50% chance of being a carrier for SCA trait
What will the hereditary pattern be like for SCA if both parents are Heterozygous recessive for SCA trait?
50% chance of having the trait/being a character for the kids
25% chance the kid will have SCA
25% chance the child is normal with no trait or disease
How does SCA incidence differ between gender?
It does not since it is not sex linked
Lifespan of a normal RBC
120 days
Lifespan of a sickle cell
15-20 days
What is the structure of an RBC with normal Hgb?
smooth surfaced, flexible, disk that can mold its shape to move through arterioles, capillaries, and venules
What is the structure of an RBC with Hgb S?
Rough textured, rigid, elongated crescent shaped RBC
RBCs with Hgb S can only ___ and __ a certain amount of times
sickle and desickle
The process of sickling is reversible at first, but cells become susceptible to …
permanent entrapment by the macrophage system of the spleen and liver (can lead to impaired filtering)
What does entrapment of sickle cells by the macrophage system cause?
Hemolytic Anemia (increased destruction of RBCs resulting in Hgb deficiency)
Manifestations of SCA
Slightly jaundiced from hemolysis (sclera yellow, urine dark)
Painful excruciating crises / intense pain caused by vascular occlusion during sickling episodes
Sickling occurs more so in certain areas
Hypoxia from systemic anemia
Serious bacterial infection d/t inadequate splenic filtering of microorganisms
Potential Splenomegaly
What causes the Jaundice of SCA?
The destruction of RBC (since they have a shorter lifespan) leads to higher bilirubin levels causing jaundice, yellow sclera, and dark urine
Bilirubin can also cause brain damage
What is the cycle and cause of the painful excruciating crises in SCA?
VASCULAR OCCLUSION - which occurs from obstructions of sickled cells –> this decreased oxygen perfusion –> Which further increases sickling in the hands, feet, abdomen, back and joints causing intense pain from lack of oxygen
Where is sickling most apt to occur?
- Areas where blood flow is slowest (liver, spleen, kidney medulla)
- In tissue with high metabolic rate (brain (stroke) and muscle)
Systemic signs of anemia lead to …
hypoxia
Why is bacterial infection more likely in SCA?
Because the spleen gets inadequate filtering ability / filtering system damaged
Splenomegaly and SCA
As the spleen has to overwork and keep removing dead cells (potentially leading to acute crisis) –> progressive infarction from no blood occurs in the spleen leading to atrophy
Can just be enlargement or cause death and atrophy
What is the most common Hgb and healthiest in normal people?
Hgb A
Why are infants asymptomatic for SCA for 4-6 months?
It is due to presence of Fetal hemoglobin
Hgb F has a higher affinity for O2 than A
What is done for a diagnosis of SCA?
Step 1. Newborn screening for hemoglobinopathies are used to ID high risk individuals (via a stained blood smear to show sickle cells)
Step 2. Hgb Electrophoresis is used to ID presence of Hgb S and CONFIRM THE DISEASE
Step 3. Serial blood tests show blood abnormalities
Alternative 1: Can occur before 1, but prenatal testing can ID the presence of the homozygote state of the fetus
What is used to confirm SCA disease ?
Hemoglobin Electrophoresis
What may serial blood tests demonstrate in an SCA patient?
Decreased Hct
Decreased Hgb
Decreased RBC
Cure for SCA?
There is not really a cure, but you could try bone marrow transplant
What kind of drugs are available for SCA?
there are not really any drugs specifically for SCA other than Hydroxyurea
Hydroxyurea
Drug for SCA that increases the solubility of Hgb S - making the cell less likely to sickle
Given to babies who are positive for SCA or for treatment in adults
What is treatment like for Symptomatic SCA adults?
There is no compound to reduce or stop sickling and no special diet vitamin or iron therapy
So, it is a “band aid” approach that is mostly about prevention of symptoms or pain relief
What sort of treatments are given to people with SCA?
Pain relief requiring potent narcotic analgesics (Since SCA is very painful)
Transfusions during crisis, to promote healing post-ulcer, or during the last trimester of pregnancy
Pneumovax vaccinations
Prophylactic antibiotics (d/t spleen function impairment)
Increased hydrations during crisis
Hydroxyurea
Avoidance of precipitating factors
Bone marrow transplant
For parents: Genetic counseling
Potential Complications arising from SCA
Vaso-occlusive events
Splenic Sequestration
Stroke
Aplastic Crisis
Avascular Necrosis
Priapism in Males
What do Vaso-occlusive events cause?
tissue infarction with intense pain and disability
What does Splenic Sequestration cause?
Hypovolemia
Shock
Death
It is a plugged, enlarged, at greater risk for infection and potential rupture, and broken filter kidney
What can stroke lead to?
Weakness
Seizure
Inability to speak
Aplastic Crisis
Bone marrow needs blood flow to make blood, so it will stop functioning without it which can eventually lead to avascular necrosis
bone marrow temporarily stops erythropoiesis
Avascular Necrosis
Long bones of the leg or arm die from occlusion leading to a need for something like a hip replacement
Priapism
Males only
Painful prolonged penile erection lasting hours, days, or weeks d/t stasis and occlusion –> usually results in impotence if now extracted
Sickle C Disease
A sickle cell disease
Recessive Autosomal
Occurs later in life, with less severe painful crises and it occurs less frequently than SCA - this is d/t Hgb C being a little less prone to sickling
Not as severe as SCA
50% of Sickle C disease patients have episodes of what?
Abdominal or Musculoskeletal pain before age 10 and moderate anemia (Hgb 8-10 gm/dL)
What else is a Sickle C disease person at risk for?
Increased risk for infection and fever which can lead to crisis
What are some Complications from Any Sickle Cell Disease?
Splenomegaly
Cardiomegaly (less blood flow and working more causes diastolic problems)
Acute Chest Syndrome
Sickle Retinopathy
Decreased Vision
Pregnancy issues
Acute Chest Syndrome
Characterized by Atypical pneumonia resulting from pulmonary infarction (d/t no oxygen in the lungs)
Second leading cause of Sickle Cell hospitalizations
Sickle Retinopathy
Blockage of blood flow to the eyes leading to blindness from retinal detachment (60-70% of patients)
When is decreased visual acuity first noticed in sickle cell patients?
at 20-30 years of age
What are some potential pregnancy issues caused by Sickle cell disease?
Severe bone pain crises
high incidence of abortions, stillbirth, and neonatal death
___ is the key for sickle cell disease
Prevention
Hemophilia
disorder of blood clotting
It is a hereditary sex linked recessive disease resulting in either a deficiency of Factor VIII (A) or Factor IX (B)
It can be mild moderate or severe depending on clotting factor percentages
Types of Hemophilia and their prevalence?
A - “Classic hemophilia” - 80%
B - “Christmas Disease” - 20%
Hemophilia is very rare to find in ___
females
Prevalence of Hemophilia is ___ in ___ Male Births
125 in 1 million
Which clotting factor is missing in Hemophilia A?
Factor VIII
Which clotting factor is missing in Hemophilia B?
Factor IX - PTC - Plasmin Thromboplastin Component
What level of Factor VIII Clotting factor leads to Mild, Moderate, and Severe Hemophilia A?
Mild - 6-30%
Moderate - 2-5%
Severe - <1%
Children with SEVERE Hemophilia A…
rarely survive childhood, experience a life of pain if they survive, have immobility and social isolation as a result
<1% Factor VIII in these children
What chances for hemophilia A does a child have if the mother is a carrier and father does not have the trait?
25% chance of a normal boy; 25% chance of normal girl
25% chance of carrier female
25% chance of Diseased male
What chances for hemophilia A does a child have if the mother is a carrier and father does does have the trait?
25% chance of afflicted female; 25% chance of afflicted male
25% chance of carrier female
25% chance for normal male
What chances for hemophilia A does a child have if the mother is not a carrier but the father does have the trait?
50% chance for carrier female
50% chance for non affected male
What chances for hemophilia A does a child have if the mother is affected and father does not have the trait?
50% chance for carrier female
50% chance to have an affected male (100% of males are affected)
What is the only situation where a female can be born with hemophilia?
If the mother is a carrier and the father has the disease (25% chance)
What is the main manifestation of Hemophilia A?
Spontaneous or Excessive Bleeding and Hemarthrosis
What are some examples of spontaneous or excessive bleeding in a Hemophilia patient?
Severe episodes provoked by minor trauma
Fatal intracranial hemorrhages with minor head bumps
Deep hematomas especially along the fascia resulting in compartment syndrome
Hematuria, Hematemesis, Tarry stools
*Minor bumps can be permanently debilitating
Hemarthrosis
Bleeding into the joints
IN hemophiliacs, joint swelling, degenerative changes, pain, limited ROM, permanent disability especially in the elbows, knees, and ankles can all occur
Compartment Syndrome
This is when the hematoma causes muscle tissue to get between the muscle and fascia preventing stretch eventually causing the muscles to die and nerves to become compromised
Diagnostics for Hemophilia A
Look for PROLONGED PTT (Partial Thromboplastin Time) - checks for clotting
See a decreased Measurement of Factor VIII
Prenatal Testing
Treatment for Hemophilia A
Factor VIII administration from fresh frozen plasma concentrate or cryoprecipitate
Complications arising from Hemophilia A
Intracranial Hemorrhaging
Infection with HIV (pre-blood screening)
Very risky to perform surgery - even dental
Where does Factor VIII need to be before, during, and after surgery?
greater than 30%
administer Factor VIII to achieve this
90% of coagulation disorders relate to ___ ___
platelet dysfunctions
What is the first line of defense against accidental blood loss?
Platelets
How long do platelets circulate for?
Normally circulate for 8-10 days then are destroyed by macrophages in the liver and spleen
At anyone one time ___ platelets are in slow transit in the spleen and do not figure into platelet count?
1/3 - only platelets in the blood matter
What happens to platelet count if there is no spleen?
There is a higher platelet count since the normal 1/3 is now in circulation. (also higher risk for stroke, clotting, thrombus, and infection)
Normal Platelet Count
150,000-400,000 cells per microliter
Platelet count is usually higher in ___ patients
Splenectomized
How does sympathetic input into the spleen impact platelet levels?
Stress –> release of EP –> splenic contraction –> release of platelets into circulation (potentially to deal with trauma)
Platelet count is low in people with Splenomegaly, why?
There is increased trapping in slow transit (in the spleen) of platelet
OR
There is increased macrophage destruction of platelets occurring
Classic Manifestation of Low Platelet Count
Petechiae
What causes low platelet Petechiae?
Loss of normal endothelial plugging (does not mean deep hemorrhaging is occurring)
It means that the normal platelet cell wide block between normal endothelial blood cells is not blocked so RBC can leak through and cause the petechiae
At what platelet count should the patient be on bleeding precautions (No IM, shaving, toothbrush, etc) for Severe and Rare spontaneous hemorrhaging?
Less than 20,000 cells per microliter
Main 2 Types of Platelet Disorders
- Quantitative (Thrombocytopenia)
- Qualitative (Thrombocythemia)
Thrombocytopenia
Decreased number of platelets (Quantitative disorder)
Possible Responsible Mechanisms for Thrombocytopenia
- Decreased or defective platelet production in bone marrow
- Decreased platelet survival (Idiopathic Thrombocytopenia)- increased destruction outside the bone marrow caused by an underlying disorder
- Sequestration (pooling of blood in the spleen or increased amount of blood in a limited vascular area)
- Intravascular Dilution (With IV fluids lowering per unit volume)
- Blood loss - hemorrhaging
The most common kind of Thrombocytopenia
Idiopathic Thrombocytopenic Purpura
Idiopathic Thrombocytopenic Purpura
Autoimmune issue where the spleen becomes a site of immunoglobulins and increased phagocytosis of platelets
2 forms: Acute and Chronic
Acute Idiopathic Thrombocytopenic Purpura
“Post Viral Thrombocytopenia”
Usually affects children between 2 and 6
Usually post virus where the antibodies can fit the virus AND the platelets leading to destruction
Chronic Idiopathic Thrombocytopenic Purpura
“Essential or Autoimmune thrombocytopenia”
Usually affects adults < 50
Especially in women 20-40 yo
Manifestations of Thrombocytopenia
Petechiae
Purpura
Ecchymosis (color changes)
Menorrhagia
Bleeding in the eyes (subconjunctival hemorrhage), ear pain, epistaxis, bleeding of gums, hemoptysis, frank or occult blood in stools, painful joints, mental status changes
Petechiae
Small spots of subcutaneous bleeding
Purpura
Large areas of subcutaneous bleeding
Menorrhagia
Excessive menstruation
Hemoptysis
Coughing up blood
Frank Blood in Stools
Bright red blood in stools added past digestion in the stomach
Occult Blood in Stools
Digested and Black stool from digested blood
When is thrombocytopenia most common?
In children, usually preceded by viral infection - it is acute and usually resolves spontaneously
Therapeutic Supports for Thrombocytopenia
Platelet Transfusions
Corticosteroids
Protection from Trauma
What are some other causes for Idiopathic Thrombocytopenia
Megaloblastic Anemia
Chronic Alcoholism
Viral Infections like HIV
Ionizing Radiation exposure
Neonate Issues
Liver Cirrhosis
Lymphoma
Metastatic Cancer
What sort of in neonate causes can lead to thrombocytopenia?
- Maternal drug ingestions
- Maternal immunoglobulin attacking fetal platelets
- congenital syphilis
- maternal viral infection
Why does Liver Cirrhosis cause thrombocytopenia
spleen enlarged with blood not flowing through the damaged liver which can lead to increased macrophage destruction
Why does Lymphoma cause Thrombocytopenia
Cancer of the lymphoid tissue enlarges the spleen so 80% of the platelets get trapped there
Why does metastatic cancer cause thrombocytopenia?
Infiltration of bone marrow can stop creation of platelets and megakaryocytes
Examples of Drugs known to Decreased Platelet Count
Cancer chemo
Thiazide Diuretics
Quinidine
Quinine
Digitoxin
Methyldopa
Sulfonimines
Gold
ASA
Heparin
Diagnostics for Thrombocytopenia?
- PLT< 20,000 cells/microliters
- Mean Platelet Volume (Size) Decreases
- Bone marrow function (Abundant megakaryocytes)
- Humoral tests to measure platelet associated IgG levels (non specific)
What can Mean Platelet Volume tell us?
It is the size of an average platelet
Bigger platelets are usually younger and aggregate better, while older ones are smaller
This may help provider determine whether to give platelet infusion or not
What does a low MPV indicate
Older platelets that do not function as well
What can raised IgG levels tell us on a humoral test for platelet associated IgG levels?
It is a non specific test, but it can give a clue toward immune mediated thrombocytopenia
What is treatment like for Kids with thrombocytopenia?
It is more conservative treatment with support in the post-viral period
What is treatment like for adults with thrombocytopenia?
- Prednisone
- Immunosuppressants (to stop the attack against yourself)
- Splenectomy if treatment is ineffective
- Immune globulins postoperatively
Prednisone
Med given to thrombocytopenia patients
it suppresses phagocytosis, promotes capillary integrity, and enhances platelet production
What is the problem with splenectomy for thrombocytopenia treatment?
- they become susceptible to infection and need their vaccines like Pneumovax
- Post splenectomy thrombocytosis can occur - prevent thromboembolic complications by giving prophylactic heparin
What are immune globulins (given postoperatively) for regarding thrombocytopenia?
It raises platelet count quickly in a short period of time (in 1-5 days but only lasts 1-2 weeks) - short term fix
Tjhrombocythemia
Quantitative platelet disorder
Increase in the number of platelets
It is associated with an increased risk for thrombosis and clotting of the vasculature
What may be some complications that occur d/t Thrombocythemia?
Stroke
Myocardial infarction
Pulmonary embolism (seen via resp distress)
DVT
When is DVT often seen?
in pregnancy
What does DVT with no explanation mean?
It is a red flag for cancer
Causes for Thrombocythemia
Iron deficiency anemia
Polycythemia vera
acute stress response
metastatic cancers
chronic inflammatory diseases
splenectomized patient
oral contraceptives (especially in smoking women)
How does Anemia lead to Thrombocythemia
It causes bone marrow to go into high gear and make more RBC, WBC, and platelets
How does Polycythemia Vera cause Thrombocythemia
overproduction of RBC and platelets occur
What kind of things can lead to an acute stress response responsible for causing Thrombocythemia?
Exercise
Post Partum
Trauma - s/p homorrhagia
Surgery
What is important to look out for after surgery with thrombocythemia?
DVTs from increased clotting - look for warmth, deep pain, red color
could dislodge and become an embolus and lead to stroke or pulmonary emboli
On day ___ post-op the patient is at highest risk for thrombocythemia
day 10
What is an example of a chronic inflammatory disease leading to thrombocythemia?
Rheumatoid Arthritis
How does metastatic cancer lead to thrombocythemia?
it increases bone marrow production
Thrombocytopathy
Qualitative platelet disorder
Normal amount of platelets, but they do not aggregate like they should
What can cause Thrombocytopathy?
- Drugs like ASA, antihistamine, and NSAIDS
- Chronic Renal Failure - toxic effects of retained urea saturated blood cells and inhibits platelet aggregation
What can we use drugs like ASA, antihistamines, and NSAIDs for knowing it can decreases aggregation?
We can use it to lower thrombus risk by lowering aggregation
There are ___ clotting factors
13
What is the purpose of fibrin?
To work as cross bridges between platelets to stabilize and cause a platelet plug
Platelet Aggregation Steps
- Vessel is damaged from some event - cascade initiated
- instantaneous accumulation at the site d/t smooth endothelium attracting platelets
- platelets release substances
- undamaged endothelium released prostacyclin and nitric oxide
5-final: clotting factor X makes prothrombin into thrombin which cleaves fibrinogen into fibrin
What do platelets attach to in order to release Serotonin, ADP, and Other Chemicals?
Proteins - Von Willebrand Factors
What does Serotonin do for bleeding?
causes vasoconstriction to decrease bleding
What does Serotonin, ADP, and Other chemicals ultimately do for platelets?
it transforms the platelet slipper disc shape into sticky spheres that form the platelet plus
Thromboxane A2
chemical released by platelets that attracts more platelets to an area
What does Fibrinogen do?
It cleaves to fibrin and connects between exposed sites in platelets like a bridge –> thus stabilizing the plug
To prevent unimpeded platelet aggregation, what must happen?
Undamaged endothelial cells release Prostaglandin I2 and Nitric Oxide
What does Prostaglandin I2 (Prostacyclin) and Nitric Oxide do in the clotting cascade?
It causes vasodilation and inhibits platelet aggregation in areas where it should no aggregate
Final step of the coagulation cascade
production of stabilized fibrin
Coagulation reactions involve…
a series of 13 coagulation factors (proteins) that are activated in a domino manner which leads to coagulation (clotting) of the blood
Coagulation Pathways?
Extrinsic Path
Intrinsic Path
Common path
Extrinsic Pathway
normally coagulation occurs first through this pathway
this is activated by trauma to a blood vessel or surrounding tissue
Need extrinsic compounds found outside the blood to work
It is responsible for clot formation in response to tissue injury
Intrinsic Pathway
A formation of a clot in response to an abnormal vessel wall in absence to vessel injury
Begins in circulation
Common Pathways
When the intrinsic and extrinsic pathways merge at factor X
Which clotting factor is responsible for converting the plasma protein prothrombin into thrombin
X (10)
___ is the master regulator of the coagulation cascade and is the catalyst for fibrin that stabilizes the clot
Thrombin
Which coagulation pathway is slower?
Intrinsic Pathway (begins in circulation as blood comes into contact with collagen in the injured vessel wall)
Clotting Factors
Proteins that are synthesized in the liver
So, if there is a liver disease, there are less factors made
Which pathway is effected by Hemophilia A and B?
Extrinsic Pathway (Factor 9 and 8 are in that path)
Why do we give a Vitamin K shot at birth?
VitK is needed for clotting, and a newborn does not have the bacteria in the gut yet to produce it and they are a bleeding risk
What clotting factors need Vitamin K?
Factors 7, 9, and 10 (and prothrombin)
Coumadin
Anticoagulant
This interferes with the vitamin K clotting factors to prevent clotting
How do we measure how much coumadin is needed?
we take a PT to know
Since Factor 10 helps prothrombin become thrombin it is PT viewed in Vitamin K factors
Heparin
Anticoagulant
Works on Non Vitamin K Factors and uses PTT time to measure heparin therapy
Both Heparin and Coumadin…
extend bleeding time
Disseminated Intravascular Coagulation (DIC)
Clotting and Hemorrhaging occurring in the vascular system simultaneously
rare, but almost always fatal
happens everywhere in the body
It is basically a clotting event that spreads alongside hemorrhaging
What does DIC cause?
Small blood vessel blockage
Organ tissue damage
Necrosis
Depletion of clotting factors and platelets
Activation of fibrinolysis which can lead to severe hemorrhaging
Organ impacts: kidney, brain, lungs, pituitary and adrenal glands, GI mucosa
What will running out of the clotting factors and platelets cause in DIC?
no ability for endothelial plugging, eventually you will bleed from every oriface and death occurs (usually when the heart does not get enough blood)
Why can we not give Heparin to a DIC patient
they are already bleeding! don’t extend that!
Also you cannot give clotting factors since that’s also already happening
Causes for DIC
Infection (septicemial, viral, fungal, protozoal)
Obstetric Complications (abruptio placentae, post partum hemorrhage)
Neoplastic Disease (acute leukemia, metastatic cancer, lymphoma)
Disorders that produce necrosis (burns, transplant rejection, liver necrosis)
Shock
Transfusion reaction
DKA, PE, SCA, ARDS
What is the pathophysiology pathway for DIC?
1 Coagulation System Triggered
- Excess fibrin forms and becomes trapped in microvasculature along with platelets –> leading to clots
- There is decreased blood flow to the tissue following a clot –> causes acidemia, blood stasis, tissue hypoxia –> all of these lead to organ failure
- Fibrinolysis and Antithrombotic mechanisms activate for anticoagulation to occur
- Platelets and coagulation factors are consumed and hemorrhaging will then begin
What value of PLT indicates DIC
<100,000 cells per microliter
What value of Fibrinogen indicates DIC
<150 mg/dL
What value of PT indicates DIC
> 15 seconds (these are the Vitamin K factors)
What value of PTT indicates DIC
> 60-80 seconds (these are the non Vit K factors)
Other than PLT, Fibrinogen, PT, and PTT values, what else can diagnose DIC?
Fibrin Degradation Products and a D Dimer Test (both measure for fibrinolytic system waste)
What value of Fibrin Degradation Products (FDP) indicates DIC
> 45 mcg/mL
What is a positive value for a D Dimer Test, checking waste of the fibrinolytic system that breaks clots down, for DIC?
< 1:8 dilution
Treatment for DIC
- Prompt treatment of underlying disorder (earlier is better)
- If there is active bleeding administer fresh frozen platelets, platelets, and packed RBCs
- (Controversial) Heparin Therapy if early enough
Why is Heparin therapy for DIC controversial?
It requires a delicate balance between clotting factors and clot busting drugs
If used early in the course of DIC it may prevent micro clotting, but its not useful later on and could exacerbate problems
Heparin therapy, in most cases, is administered with…
transfusion therapy
Fibrinolysis
“Clot Busting System”
Components of the Fibrinolytic System
Plasminogen
Plasmin
Urokinase
Tissue Plasminogen Activators (TPA)
Plasminogen
Present in plasma
a plasmin precursor
acted upon by activators like urokinase present in tissues, endothelial cells, and granulocytes which detect presence of a clot
Plasmin
Also called fibrinolysin
active enzyme (protease) that cleaves or lyse fibrin or fibrinogens to soluble fragments that in turn binds fibrin monomers preventing further polymerization (prevents the fibrin cement for the plug)
cleared by the liver
Urokinase
Protein secreted by kidney cells that directly activate plasminogen into plasmin
can be given IV, 6 hours after an MI, and can be used to break down pulmonary emoboli
Tissue Plasminogen Activators (TPA)
Compounds only active only in the presence of fibrin
Helps activate Plasminogen
Can be used to stop an embolic stroke and de clot a central line
Which kind of Stroke can TPA be used for
Embolic Stroke
*NOT Hemorrhagic, that would make it worse
How can TPA be useful with a central line?
If you are unable to draw up blood from the line that’s supped to get big pollutants out of the heart, you can use this to break up the fibrin sheathe at the end of the line and prevent having to put in a new surgical line
Clotting occurs at the same time as de-clotting to allow
clotting localization
What does the Fibrinolytic System do?
Breaks up existing clots
It lyses fibrin and causes inactivation of fibrinogen via factors
It also interferes with platelet aggregation and increases time needed to convert prothrombin to thrombin (inhibition of further clot formation)
Measure FDP to determine effectiveness
Which factors does the fibrinolytic system impact?
Facto I
Factor V
Factor XIII
Why does DVT need natural body healing rather than massage or heparin?
Those things can prevent further clots or dislodge the clot but cannot care for existing clots
the plasmin the body can break down existing clots though
What value is often used instead of PT and PTT?
INR
What is a normal INR value
1
What value should INR be for mild clot prevention? Aggressive clot prevention?
mild - 2.5
aggressive - up to 4
*INR is 2-4x higher when trying to anticoagulate someone
Warfarin
Generic name for Coumadin
Measure PT with this since it impacts VitK factors
More Vit K = decreased effectiveness
Need proper Vit K Amounts
Lovenox
low weight form of heparin
Measure PTT since it affects non VitK dependent factors
people can go home with this form
What is the antidote for Lovenox/Heparin?
Protamine Sulfate
What is the antidote for Warfarin/Coumadin?
Vitamin K
The goal of anticoagulation is ___
balance
