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
