Clinical Clotting Disorders Flashcards
Primary vs. Secondary Hemostasis
Primary- is a function of the platelets
Will result in multiple, tiny, superficial hemorrhages. Ex. Petechaie, purpura (large petechaie), ecchymoses and mucocutaneous bleeding
Secondary- dependent on the clotting factors.
Will develop deep tissue bleeding such as hematomas or hemathroses
Primary Hemostasis
Consists of platelet plug formation, vascular spasm, and capillary endothelial adhesion, with capillaries collapsing and sticking closed when empty. This is a temporary fix and lasts for only 12-24 hrs.
This is why hemophiliacs often do not bleed until 12-24 hrs after trauma.
ASA- irreversibly acetylates cyclooxygenase, decreasing platelet function. Chronic ASA use (as little as 40mg/d) will suppress 95% of thromboxane A2.
NSAIDS- bind reversibly with cyclooxygenase.
Clopidrogrel (Plavix) irreversibly inhibits ADP binding to the platelet receptor resulting in decreased platelet aggregation
Secondary Hemostasis
As the platelets are aggregating, the clotting pathway is activating.
Indices
PT- Extrinsic pathway and common pathway
PTT- Intrinsic pathway and common pathway
Platelet count
Platelet function tests- evaluate platelet aggregation when stimulated by epinephrine, ADP and collagen
Causes of Primary Hemostasis
Production Defects- Due to bone marrow failure from toxins, infiltration, aplasia, sepsis, HIV
Hypersplenism
Survival defects:
Consumptive- DIC, HIT, TTP/HUS, HELLP
Autoimmmune- ITP ( either idiopathic or drug induced). Common drugs are heparin, rifampin, sulfa, digoxin and acetaminophen
Idiopathic Thrombocytopenic Purpura (ITP)
ITP is an acquired disorder leading to immune-mediated (IgG) against platelet Ag (GP IIb-IIIa)
Most common cause of thrombocytopenia
Acute disease: mostly children from viral infection and resolves on own
Chronic: mostly adults (women during childbearing age), and takes longer to resolve
Decreased platelets, normal PT/PTT, increased megakaryocytes (make platelets)
Mucocutaneous bleeding, normal peripheral smear and count, ecchymoses, petechiae
Tx: steroids, observation, IV immunoglobin, splenectomy
CAUSES SPONTANEOUS BLEEDING
Thrombotic Thrombocytopenic Purpura (TTP)
A disorder characterized by thrombocytopenia, a microangiopathic anemia, and laboratory evidence of hemolysis and microvascular thrombosis.
Fulminant disorder with an increase in platelet consumption.
There is a deficiency of vWF-cleaving protease activity. This leads to an accumulation of ultra large vWF multimers which can cause activation and clumping of platelets in blood vessels
TTP Symptoms
Classic pentad= FARTN
1) Fever
2) Anemia-( microangiopathic hemolytic anemia)
3) Renal Failure
4) Thrombocytopenia
5) Neurologic changes
Cause is often idiopathic but can be associated with cancer.
It is more common in women, pregnancy and in HIV cases
TTP Dx Findings and Tx
Diagnosis- findings of a hemolytic anemia such as, decreased haptoglobin, decreased Hb, increased LDH, elevated retic count and schistocytes.
The PT and PTT are usually normal.
Do not treat with platelet transfusions.
Treatment with plasmapheresis (plasma exchange) has reduced the mortatlity from 85-100% to 10-30%.
Hemolytic Uremic Syndrome
This is a syndrome characterized by
Acute renal failure
Microangiopathic hemolytic anemia
Thrombocytopenia
It is seen predominantly in children, most cases preceded by an episode of diarrhea (most often hemorrhagic).
Escherichia coli 0157:h7 is the most frequent cause.
HUS not associated with diarrhea is termed DHUS
Treatment is primarily suportive.
In DHUS: 40% of children will require some period of support with dialysis.
In HUS the mortality is
HELLP Syndrome
This is a subgroup of preeclampsia (new onset of hypertension and proteinuria after 20 weeks of gestation).
Causes a severe preeclampsia with anemia.
Can be accompanied by CNS dysfunction, BP>160/110, severe proteinuria, oliguria, ARF, pulmonary edema, ALF, thrombocytopenia or DIC
Consists of: Hemolysis Elevated Liver tests Low Platelets Anemia is microangiopathic with shistocyes.
Treatment is delivery of the fetus with no role for plasmapheresis
Heparin Induced Thrombocytopenia (HIT)
This is a drug induced thrombocytopenia due to heparin.
Occurs when an antibody is formed that recognizes heparin/platelet factor 4 complexes with resultant activation of platelets.
Is potentially fatal.
Onset of thrombocytopenia occurs within 5-10 days of heparin initiation.
Can test for HIT antibodies but the presence alone of the antibodies does not indicate HIT. 50% of patients that have had CABG surgery will develop these antibodies. Is usually most beneficial in ruling out HIT as a cause of thrombocytopenia
Heparin Induced Thrombocytopenia (HIT) Findings and Tx
The platelet counts are usually > 20,000.
Thrombosis, not bleeding is the major complication.
LE dopplers should be checked for the presence of DVTs.
Tx- Stop all heparin exposure (also lovenox) and start direct thrombin inhibitors (lepirudin or argatroban). Patients can then be transitioned to warfarin for usually 3-6 months
vWF Disease
Is the most common inherited bleeding disorder
There are 2 functions of vWF:
- It is the major adhesion molecule that tethers the platelet to the exposed endothelium.
- It is the binding protein for factor VIII, resulting in significant prolongation of the factor VIII in circulation.
Symptoms: platelet like, but severe = hemophilia A like because decreased factor VIII
Expression is variable with some patients bleeding only after surgery and others suffering bleeds of the mucosal surfaces of the GI and GU tracts
vWF Disease Tx
Usually treated with DDAVP (desmopressin). This causes the release of factor VIII and and vWF from endothelial stores. It is usually given before surgery or procedures
AML
Most common form of blood malignancy
Thrombocytopenia:
Disruption of the normal marrow processes
Proliferation of blasts
Low Platelets
Petechiae-(small-3mm) non blanching pinpoint lesions under the skin-are common
Untreated is uniformly fatal
Polycythemia Vera
This is a clonal disorder involving a multipotent hematopoietic progenitor cell in which phenotypically normal red cells, granulocytes and platelets accumulate in the absence of a recognizable physiologic stimulus.
This is the most common of the chronic myeloproliferative disorders
It appears that a mutation in tyrosine kinase JAK2 plays a central role.
Most of the time, the diagnosis is by a high Hb and HCT on the CBC. The erythropoietin level will not be elevated
Polycythemia Vera: Symptoms
Splenomegaly can also be a presenting sign.
The uncontrolled erythrocytosis can cause a hyperviscosity which can cause symptoms as: vertigo, TIA, tinnitus, headache, and visual disturbances.
Pruritus is also common.
It can also cause systolic HTN and thrombosis. PV should always be suspected in a patient with a hepatic vein thrombosis
With the large turnover of RBC’s, hyperuricemia with secondary gout can ensue.
Erythromelalgia is a symptom complex of erythema, burning and pain in the extremities, which is a complication of the thrombocytosis of PV.
Myelofibrosis and leukemia are complications
Polycythemia Vera: Tx
Phlebotomy- Hct 45% CBC every 4-8 weeks
Aspirin- Low dose to reduce thrombotic events, high dose hemorrhage
Hydroxyurea- 15-20mg/kg/day to target Hct, Increase risk leukemia
Interferon alpha- 3 mil units to target Hct, reassess at 3-4 months, side effects
Hemophilia A
Factor VIII deficiency
X-linked Recessive
The PTT is increased and the PT is normal.
The clinical presentation is easy bruising, muscle and joint hemorrhages, and prolonged hemorrhage after surgery or trauma, but no excessive bleeding after minor cuts.
Treated with DDAVP. This will cause a release of vWF and factor VIII stores from endothelial stores.
For more severe cases, treat with factor VIII concentrate
Hemophilia B
Christmas Disease (Factor IX)
X-linked Recessive
The PTT is increased and the PT is normal. The clinical presentation is easy bruising, muscle and joint hemorrhages, and prolonged hemorrhage after surgery or trauma, but no excessive bleeding after minor cuts.
Treat with human factor IX concentrate- BeneFIX
Hemophilia C
Factor XI Deficiency
Autosomal Recessive (Ashkenazic Jewish)
The risk of bleeding is dependent more on the gene mutation leading to the disorder than on the actual serum level of factor XI
Disseminated Intravascular Coagulation (DIC)
This is the most common acquired coagulopathy. It is always a secondary condition so the underlying disease must be treated for the DIC to resolve.
DIC occurs in diseases that promote tissue factor release. Ex- massive direct tissue trauma, production of TNF, sepsis, retained placental tissue and acute leukemia
DIC Lab Results
Prolonged PT and PTT Thrombocytopenia Fibrinogen decreased D-dimer increased Increased thrombin time Shistocytes and RBC fragments are found in half of the patients which indicates the microangiopathic hemolytic anemia
DIC Symptoms
The massive depletion of coagulation factors and platelets and the increased fibrin split products may result in bleeding.
The symptoms in DIC result from bleeding or microvascular thrombosis as well as the underlying disorder.
If the patient has chronic DIC, consider a solid tumor as the source
DIC Dx and Tx
Diagnosis- check the fibrinogen (will be low) and D-dimer levels (will be high).
Treat the underlying disorder or the DIC will not stop.
With severe bleeding, give FFP and platelets. Heparin is not usually effective
Vitamin K Deficiency
Vitamin K Deficiency- Vitamin K is needed for factor production.
Vitamin K dependent clotting factors are II, VII, IX, X, protein C and S.
Causes- decreased dietary intake, malabsorption, antibiotic use, and decreased storage due to liver disease.
The PT is prolonged with the PTT being normal
Warfarin Overdose
Inhibits Vitamin K epoxide reductase
Interferes with production of Vitamin K dependent clotting factors.
Initial rise in the INR (PT) will occur when the already present clotting factors will start to be degraded. This will depend on their half lives. (C & S)
Treatment is via administration of Vit K or FFP
Long half life can confound therapy
Multiple indications: A Fib, Factor V Leiden, DVT, PE…
Factor V Leiden
The most common inherited genetic clotting disorder, single point mutation
Causes a resistance to the normally inhibitory effects of protein C
VTE is common 90% (initial presentation), uncommon clot locations as well
Risk factors include; trauma, BCPs (protein C interference), immobilization
Management is via warfarin
Exsanguination
Excessive bleeding leading to hypotension, arterial dilation, low perfusion of tissues, peripheral O2 low all causing shock
Tx: clotting factors and FFP
Atrial Fibrillation
Most common SVT: unorganized depolarization causes improper contractions and stagnant blood flow, clot forms in top of atrium, clot breaks off so flows into L ventricle, aorta, common carotid, head and causes stroke
Causes: uncontrolled HTN, COPD, and MI
Treat with AV nodal blocking agents (mindful of WPW), anticoagulation, anti-arrhythmics
Warfarin at 2-3 INR, Pradaxa, Eliquis or Xarelto
Sickle Cell Anemia
Autosomal Recessive gene
Sickle Trait leads to malaria resistance (heterozygote advantage) Low [O2] leads to crisis
Defective Hemoglobin (Hb S):
Affects the cytoskeleton of the RBC
Thought to create blockages exacerbated by relatively non-pliable WBCs
Autosplenectomy and numerous infarcts
GB disease due to high levels of bilirubin
Life expectancy 50s
