Hubbard: Bleeding and Clotting DSA Flashcards
__________ = most important predictor of bleeding
risk.
History of bleeding risk
________= hallmark of moderate and severe factor 8 and 9 deficiency
Spontaneous hemarthroses
Disorders due to ABNL platelets vs coagulation facts cause WHAT findings
- ABNL platelets = Mucosal/skin bleeding => peteechiae
2. ABNL coagulation factors = JOINT bleeding, deep tissue bleeding
How does bleeding due to clotting factor abnormalities differ from those seen with platelet deficiencies?
- Spontaneous petechiae/purpura = uncommon
- Bleeding manifests as large excxymoses or hematomas after injury or prolonged bleeding after laceration/surgery.
- Often occurs into the GI/GU tracts and into weight-bearing joints (hemarthrosis)
_______ = suggestive of underlying
platelet disorders or Von Willebrand disease (VWD), also called disorders of primary hemostasis or platelet plug formation.
Mucosal bleeding symptoms
Bleeding symptoms that appear to be more common in patients with
bleeding disorders include …
- Prolonged bleeding with surgery
- Dental procedures and extractions, and/or trauma
- Heavy menstrual
bleeding (HMB) - Postpartum hemorrhage (PPH)
- Large bruises (often described with lumps).
\_\_\_\_\_\_ = MC symptom in hereditary hemorrhagic telangiectasia (HHT) and in boys with VWD
Epistaxis
Bleeding with eruption of primary teeth = common in _________
Kids with severe bleeding disorders (moderate - severe hemophilia)
Heavy menstrual bleeding = loss of ______ of blood per cycle, based on the quantity of blood loss required to produce iron-deficiency anemia
> 80 mL
Complaint of heavy menses is subjective and poorly correlates with excessive
blood loss. Predictors of HMB include bleeding resulting in: (4)
- Iron-deficiency anemia
- Need for blood transfusion
- Passage of clots >1 in. in diameter,
- Changing a pad or tampon more than hourly
HMB is a common symptom in women with underlying
bleeding disorders and is reported in the majority of women with
- VWD
- Factor XI deficiency, and symptomatic carriers
of hemophilia.
_________
has been associated with angiodysplasia of the bowel and GI bleeding.
VWD, particularly types 2 and 3
Hemarthroses and spontaneous muscle hematomas are
characteristic of __________
Moderate - severe congenital factor 8 or 9
deficiency
Muscle and soft tissue bleeds are also common in ______
factor 8 deficiency
Life-threatening sites
of bleeding include bleeding into the
- Oropharynx
- CNS
- Retroperitoneum
_________ bleeding is the
major cause of bleeding-related deaths in patients with severe congenital factor deficiencies
CNS
What medications and dietary supplements have pro-hemorrhagic effects
- ASA and NSAIDS that inhibit COX-1 => impair primary hemostasis
- ADP P2Y12 inhibitors (-grel drugs) = inhibit platelet aggregation & have higher risk of bleeding
- Fish oil/omega3 FA = INC PGI3, which impair platelet function
- Vitamin E = inhibits PKC-mediated platelet aggregation and NO production
UNDERLYING SYSTEMIC
DISEASES THAT may be present with bruising/mucosal bleeding
- Liver disease
- Severe renal impairment
- Hypothyroidism
- Paraproteineimias
- Amyloidosis
- Conditions causing BM failure.
What factors are dependent on Vit. K?
Vitamin K deficiency results in?
Factors 2, 7, 9, and 10, as well as protein C and protein S
-Bleeding
NL blood platelet count is _______
150,000–450,000/μL.
What platelet count does spontaneous bleeding occur?
<10,000–20,000/μL
At what platelet count can most surgical procedures be performed at?
50,000/μL, but preferably ~80,000/μL.
What are the major RF for arterial vs venous thrombosis?
- Arterial = atherosclerosis
- Venous = immobility, surgery, underlying medical conditions like hormonal therapy, obesity and genetic predispositions
Most important point in a history related to venous
thrombosis is determining whether the thrombotic event was …
Idiopathic (no clear precipitating factor) or
was a precipitated event.
In patients without underlying
malignancy, ___________ = strongest predictor of
recurrence of VT
Having an idiopathic event
Routine pre-op and pre-procedure testing, an abnormal prothrombin time (PT) may detect…
- Liver disease
2. Vitamin K deficiency
The most commonly used screening tests are the _________
- PT
- aPTT
- Platelet count
INR is used for what?
- Assess stable anticoagulation due to reduction of vitamin K–dependent co-ag factors;
- Liver disease.
Allows comparison between laboratories.
Mixing studies are used for what?
Evaluate a prolonged aPTT or, less commonly PT, to distinguish between a factor deficiency and an
inhibitor.
If isolated factor deficiencies => the aPTT will correct. with mixing and stay corrected with incubation. With aPTT
prolongation due to a lupus anticoagulant, the mixing and
incubation will show no correction. In acquired neutralizing factor
antibodies, notably an acquired factor VIII inhibitor, the initial assay
may or may not correct immediately after mixing but will prolong
or remain prolonged with incubation at 37°C.
How is a mixing study performed?
NL plasma and patient plasma are mixed
in a 1:1 ratio => determine aPTT or PT .
If isolated factor deficiencies => aPTT will correct.
aPTT
prolongation due to a lupus anticoagulant => aPTT will not correct.
In acquired neutralizing factor
Ab, notably an acquired factor 8-inhibitor => the initial assay may or may not correct immediately after mixing but will prolong
or remain prolonged with incubation at 37°C.
When are specific factor assays REQUIRED?
How are they performed?
When bleeding is severe
To perform: a modification of
the mixing study: mix patient’s plasma with plasma deficient in the factor being studied.
How can we test for Anti-phospholipid AB (cardiolipin Ab or B2-microglobulin)?
ELISA
What are dRVVT and TTI?
drVVT = dilute Russel viper venom test
TTI = tissue thromboplastin inhibition
Modifications of standard
tests with the phospholipid reagent decreased, thus increasing the sensitivity to Ab that interfere with the phospholipid
component. The tests, however, are not specific for lupus anticoagulants, because factor deficiencies or other inhibitors will also result in prolongation.
Documentation of a lupus
anticoagulant requires
Prolongation of a phospholipid dependent
coagulation test + lack of correction when
mixed with normal plasma and correction with the addition of
activated platelet membranes or certain phospholipids
What is thrombin time and reptilase time and when are they used?
Measure conversion of fibrinogen => fibrin
Prolonged when the fibrinogen level is low (usually <80–100 mg/dL) or qualitatively abnormal, as seen in inherited/acquired dysfibrongenemias and/or when fibrin/fibrinogen products interfere.
___________ time is prolonged in the presence of heparin.
Thrombin/reptilase time
How are the following factors affected in thrombophilia (clotting disorders)?
- Antithrombin
- Protein C/S
- Antiphospholipid AB
- Decreased (also decreased by heparin)
- Increased (decreased by Warfarin)
- AP AB (positive)
Thrombophila evaluations
How is it done?
Why?
When?
How = molecular diagnostics, immunologic and functional assays.
Why = assess need to extend anti-coagulation studies
When = in a steady state, remote from acute event. Stop warfarin after the initial 3-6 months of treatment and testing can be performed at least 3 weeks later.
Screening assays that are sensitive and specific for platelet function (platelet disorders and VWD)
- PFA-100 and similar instruments that measure platelet-dependent coagulation.
However, don’t use to predict bleeding risk or monitor response to therapy.
Venous stasis is usually due to what?
- Chronic insufficiency of the venous system (varicose veins)
- Inflammatory damage to veins (post-phlebitic syndrome)
How do patients with venous stasis typically present?
- Progressive LE edema, with achy pain in legs that worsens with standing
- Shiny, atrophic skin
- Telangiectasies
- Varicose veins
1st line of treatment for venous stasis
External compression + behavior modification (no prolonged periods of standing + leg elevation)
Treatment ulcers due to chronic venous stasis
Unna boots = specialized compressive dressing treated with agents to decrease edema + promote healing. However, must be put on by medical professional.
What are the 2 manifestations of venous thromboembolism (VTE)?
- DVT
2. PE
The syndrome of DVT includes thrombosis in which 2 areas?
- Vein in proximal leg
2. Large veins in the UE
Why is the incidence of DVT of the upper extremities rising in incidence?
Secondary to ↑ use of indwelling venous catheters
How do patients with a LE DVT usually present?
Affected limb:
- Erythema
- Swelling
- Tenderness
The initial and most important step in evaluating a possible DVT is what?
Determine the clinical likelihood of disease, so we can figure out the proper testing.
Initial assessment of DVT =
Wells score
Testing in patients with a low clinical
likelihood of DVT
D-dimer: Low clinical probability + (-) D-dimer => rules out DVT
Testing in patients with a (+) D-dimer or if clinical likelihood of DVT is high (+ Wells)
Duplex Ultrasound: excellent sensitivity and specificity for DVT
Gold standard test for DVT
Venography, but rarely used.
Who should receive prophylaxis for DVT/PE?
- Known thrombophilic condition
2. All hospitalized patients with VTE RF and no CI.
What is the most effective treatment for prevention of VTE in hospitalized pt’s with risk factors?
Pharmacologic prophylaxis
What is a pro and con of using D-dimer in the assessment of DVT/PE?
- Pro = negative test makes DVT unlikely; simple to perform
- Con = positive test is not diagnostic of DVT; other conditions can elevate D-dimer
All patients with an established DVT and no CI should undergo _______.
Immediate anticoagulation: IV unfractionated heparin or LMW heparin
Which agent is used most often for longer-term anticoagulation in pt with established DVT; describe how it’s administered and the guidelines that need to be followed?
- Warfarin
- Typically started w/ heparin and both used for minimum 5 days until INR = 2-3 for 2 measurements taken 24 hrs apart
What are some pros and cons of the newer anticoagulant agents, dabigatran, rivaroxaban, apixaban, and edoxaban?
- Oral, rapid onset, do not require monitoring or overlap w/ heparin; minimal interactions with foods and other meds
- Most cannot be used in pt’s w/ significant kidney failure
Once a patient with established DVT is on stable anticoagulation they should be treated for a minimum of how long?
3 months
If there are strong CI to anticoagulant therapy in pts with established DVT, what treatment option exists; what are some downfalls to this treatment?
- Inferior vena cava filter
- Will ↓ likelihood of PE in short-term, but they may actually ↑ the long-term risk of recurrent DVT
Should patients at risk for VTE be screened for DVT or PE (ex. via D-dimer)?
No: insensitive and does not improve clinical outcomes
Most common symptoms of PE
- Dyspnea
- Pleuritic chest pain
- Cough
- Hemoptysis
- Tachypnea, crackles, tachycardia, and
accentuated pulmonic component of S2
In clinically stable patients (eg, outpatients without hemodynamic compromise) with a low probability of PE, what can effectively r/o a PE?
NL D-dimer
What is the indication for using D-dimer in pt’s with a higher probability of PE or clinical instability?
D-dimer testing should NOT be used to confirm or exclude the diagnosis.
Further testing is indicated.
Initial imaging test for PE =
- Contrast-enhanced CT (also called
CT angiography)*** - Ventilation-perfusion (V/Q) scanning
What is considered the gold standard screening modality for DVT/PE in intermediate cases; what are some pros and cons of using it?
- CT pulmonary angiography (CT angiography)
- Pros: high sensitivity and specificity; accurate anatomy assessment
- Cons: requires contrast (allergies, AKI), expensive, radiation exposure, and may miss small peripheral clots
What are the pros and cons of using ventilation/perfusion scans in the evaluation of DVT/PE?
- Pros: high sensitivity + inexpensive
- Cons: low specificity + may not demonstrate small sub-segmental defects
A totally normal finding using which imaging modality is the only one that can exclude PE?
V/Q scan
What would be the imaging modality of choice to use in a patient with renal failure or someone who is obese for initial assessment of PE?
V/Q scan
How are MOST patients with a PE managed?
Hospital, until stable with supportive care, including treatment of hypoxia and management of hemodynamic instability.
How should patients with circulatory shock due to PE, those with
acute embolism and pulmonary HTN or right ventricular
dysfunction but without arterial hypotension or shock be treated?
Thrombolytic therapy (clot lysis)
Treatment of patient who is
unstable and thrombolytic therapy is CI or if drug therapy has been unsuccessful.
Surgical embolectomy
Prevention of PE with an IVC filter is indicated when?
- Failure of medical therapy (evidence of PE despite adequate
anticoagulation) - CI to anticoagulant therapy
due to unacceptably high bleeding risk
Once a patient is on stable anticoagulation with PE, how long should therapy be continued?
For a duration based on the individual risk factor profile
RF for thrombosis
- Old age (>80YO)
- Surgery
- Immobilization
- PG
- Hospitilized prior to DVT
- Smoking
