COAGULOPATHIES

PeniRif, SulfAllo, QuiniLam

All cause hemolysis, thrombocytopenia, allergic interstitial nephritis, rash
Platelet bleeding with normal platelet count = vWF dz
vWF (Factor VIII antigen) and Factor VIII travel bound to each other
Will cause an increased PTT
First test is bleeding time, then ristocetin or vWF level
TX w/desmopressincauses release of subendothelial stores of Factor VIII and vWF (can only be used
once)
Note!: FFP contains all clotting agents EXCEPT Factor VIII and vWF
Glanzmann thrombasthenia, Soulier syndrome = def'y in platelet glycoprotein Ib or IIb/IIIa receptor;
presents like vWF but vWF levels are normal
Low platelets, platelet bleeding, normal spleen = ITP
Caproic acid--inhibits fibrinolysis/procoagulant, used in DIC
Hemophilia A or B: Normal PTT and elevated PT
Delayed hemarthosis in male child = hemophilia
Initial plug is with platelets; ADAMTS 13 will dissolve vWF, no fibrin plug, bleeding will start
First test is PTT, then mixing study
o Mix normal blood and see if PTT normalizes
If yes, factor deficiency is present
If no, inhibitor/Ab is present
Third test is Factor VIII def'y (for hemophilia A)
o Hemophilia A is 10x more common than hemophilia B (factor IX def'y)
TX w/Factor VIII (severe) or desmopressin (mild)
DIC: Platelets low, PT AND PTT elevated, bleeding everywhere
D-dimer most accurate test; fibrin split products also works
C14 Serotonin release = test for HIT, but at least 3rd-line
Hemolysis gives high LDH, high bili, high retics
TX w/FFP and platelets
Glanzmann thrombasthenia, Soulier syndrome = def'y in platelet glycoprotein Ib or IIb/IIIa receptor; presents
like vWF but vWF levels are normal
Storage pool disorder = uremia-induced platelet dysf'n
TX w/desmopressin and dialysis (incr. vWF and fVIII will incr. platelet activity)
Anticoag for PE in pts who develop HIT?
First text is platelet factor 4 Ab (heparin-dependent, against heparin and platelet)
TX w/antithrombin med = argatroban, dabigatran
Anemia/hemolysis, uremia, thrombocytopenia = HUS
Can be caused by E. coli O157H7, Shigella

Mechanism of HUS = Decrease in ADAMTS 13

o Normally dissolves vWF and frees platelets
Incr. platelet clotting, RBC fragmentation as they break against fixed platelet strings
Normal PT and PTTdistinguish from DIC with coag tests
o DIC presents with the above but elevated PT and PTT
o Caproic acid inhibits fibrinolysis/procoagulant, used in DIC
Decreased haptoglobin
TX: Mild HUS, supportive care; in severe HUS, FFP
o NEVER give abx or platelets
Clopidogrel can cause TTP or HUS (so can ticlopidine, removed from market)
TTP will present with the above + fever and CNS def'y
DIC presents with the above but elevated PT and PTT

Fibrin activated by thrombin and destroyed by plasmin

Fibrin necessary to stabilize platelet-vWF clots
PTT = VIII, IX, XI, XII
Never do antiplatelet Ab testing

ACROMEGALY
Bone growth, daytime somnolence, bad odor, deepening voice
Growth of bony structures as well as cartilage
Sleep apnea d/t growth of soft tissues of the neck (thickening), not obesity
IGF1 and GH both decrease adipose
Raises lipids (as FFAs/LDL) and sugars while building protein
Wide-spaced teeth, d/t bone growth in jaw (teeth cannot grow once enameled)
Acromeg does not cause caries (which increase in Sjogren syndrome d/t sicca syndrome), gingival
hyperplasia, or thrush
Malodor d/t sweat gland hypertrophy
Hyperplastic colonic polyps, but no increase in frank colon cancer (vs. dysplastic premalignant polyps)
Erectile dysfunction in men d/t increased prolactin
Prolactin inhibits GnRH secretion from hypothalamus
o Alpha subunit of GH is identical to prolactin, and 20-40% of people with acromeg have a cosecreting prolactinoma
Causes amenorrhea and galactorrhea in women
Ca and BPH don't cause ED
TX w/bromocriptine (dopamine agonist)
Bilateral thenar eminence wasting d/t carpal tunnel
Increased protein synthesissoft tissue enlargement in wristsmedian nerve entrapment
Diabetes in acromeg d/t anti-insulin effects of GH
To find abnormalities in GH, look for IGF1 elevation
Only peptide hormone that has a protein carrier
o Longer half-life and constantly elevated
GH only elevated from 2-3am
Follow with glucose suppression testing

GH should fall w/admin of glucose; but this is not the first test
Never do imaging first in endo
o 10% of population have pituitary abnormalities, most of which are nonfunctional
o Ditto 4% adrenal abnormalities

TX: First, transsphenoidal surgery

Surgery will cure 50-70%
Effects on bone and cartilage will not improve
Can also try pegvisomant (GH receptor blocker, blocks both stress-hormone and IGF1 effects)
Bromocriptine, cabergoline (dopamine agonists)
Octreotide (somastatin analogue)
Complications of transsphenoidal pituitarectomy
Hypernatremia d/t central diabetes insipidus
o Loss of ADH, synthesized in hypothalamus and stored in posterior pituitary
NO hypokalemia, cardiovascular collapse, increased HR
o Aldosterone is controlled by angiotensin, which is produced in the liver (angiotensinogen)
NO immediate hypothyroidism
o T4 has a long half-life, and there is several weeks' reserve of T3 in the thyroid
NO effect on Ca2+, which is controlled though the parathyroids
50% of people with acromegaly have htn and DM
Life expectancy under age 50die of dilated cardiomyopathy and accelerated atherosclerosis
o Joints also grow out of alignment; most past age 45 have severe physical disability
Treated acromegaly/drop in GH will improve BP over time, mechanism unknown
o If no surgery, octreotide and pegvisomant will also improve htn
Adolescent boy w/short stature and low GH and IGF levels?
Next test: TSH
o Must have thyroxine for GH release ('cretinism' is d/t hypothyroidism)
52y/o M w/unclear abnormal facial features?
Equivocal cases use functional test for acromegaly: Response of GH to glucose
o Should suppress GH
Adenomatous disease is a failure to respond to feedback
o Insulin admin should cause GH to rise; if GH does not respond, panhypopituitarism
o High T4 and high TSHTSH-producing tumor
o High acid level and high gastringastrinoma
o High cortisol and high ACTHACTH-producing tumor

Angiodysplasia is the second most common cause of dysplastic bleeding in older adults
Paget'sAffects skull and long bones without affecting cartilage
Cushing'sDoes not cause bone abnormalities; primarily redistribution of fat and transformation of tissue to
sugar
LeishmaniasisSOB, LVH, MI, hepatosplenomegaly, cardiomyopathy via tsetse fly
Mycosis fungoidesCutaneous T-cell lymphoma

MITRAL STENOSIS
S2click/soundmurmurS1 = diastolic decrescendo murmur
LA pressure > LV pressure = open mitral valve
o LA pressure increases in MS
Opening snap gets earlier in diastole the worse the lesion (diastole shortens)
o S1 is also louderhalf-open at beginning of systole, then slams closed
Rheumatic fever hx, cough, hemoptysis in a young person
Presents after any sudden increase in plasma volume or cardiac output, incl. preg., heavy exercise or
severe infx
o Preg = 50% incr. in plasma volume + automatic anemia
o Heavy exercise or severe infxns incr. CO
More likely an immigrant
o Rheumatic fever cases lack access to care/abx for pharyngeal strep infx; rare in the US
Mechanism of hemoptysis in MS: Pulmonary hypertension
o Chronic hypoxia causes pulmonary vasoconstriction, as does the increased back-pressure of a
stenotic valve
o Both increase hydrostatic pressure and chances for capillary rupture
Mitral stenosis DOES NOT affect LV funx/size
Can cause dysphagia and hoarseness d/t left atrial hypertrophy
o Pressure on esophagus and left recurrent laryngeal nerve
o CXR: Straightening of L heart border, pushing up of L mainstem bronchus
Most accurate test = L heart cath
First diagnostic is echo
TX: Initial therapy = diuretic, salt reduction
NOT ACEis/ARBsthey help with emptying, not filling
Digoxin's only use in mitral stenosisslows HR in afib to allow for more ventricular filling time
o Also use BBs and CCBs for same purpose
Definitive TX is balloon valvuloplasty
o Valve replacement only if this fails
o Aortic valves get replaced as first-line tx in AS
Aortic stenosisSystolic (S1S2) crescendo-decrescendo murmur radiating to carotids
Should hear S1 & S2
Older adult w/syncope, angina, CHF
Aortic regurgDiastolic (S2S1) decrescendo mumur at LL sternal border
Can hear S1 at end
Water-hammer pulse, SOB, LVH, MI, dilated cardiomyopathy
Can be secondary to valve or chordae tendonae rupture
Mitral regurgHolosystolic (S1S2) murmur, constant, radiating to axilla
Obliterates S1 & S2
SOB, MI, dilated cardiomyopathy
Can be secondary to valve or chordae tendonae rupture
Mitral valve prolapsemurmur improves (softer) with incr. preload
Atypical chest pain, palpitations, panic attack
Pericardial friction rubConstant rub over sounds of S1 and S2

PDAPresents in infancy/childhood, continuous machinery murmur

Kussmaul signIncreased JVD on inhalation = Constrictive pericarditis or tamponade
Normally neck veins should decrease on inhalation
Pulsus paradoxusDecrease of BP by MORE than 10 points on inhalation = tamponade
Inhalation normally causes a drop in BP, but less than 10 points
May cause obliteration of radial pulse on inhalation if systolic drops below 90
S3 gallopVolume overload; sound of rapid ventricular filling
S4LVH; sound of blood hitting stiffened LV
Values in stenotic lesions
CO down
SVR increased
Wedge/LA pressure increased (on Swann-Ganz)
Pulm artery pressure increased
Decreased afterload (Amyl nitrate)
NO effect on mitral stenosis
Aortic stenosis gets louder/worse
Aortic & mitral regurg get softer/better
Increased afterload (Handgrip)
NO effect on mitral stenosis
Aortic & mitral regurg get louder/worse
Aortic stenosis gets softer/better
Increased preload (Squatting & leg raise)
ALL murmurs get louder/worse EXCEPT HOCM and MVP (get softer)
HOCM and MVP get softer
Decreased preload (Standing & Valsalva)
ALL murmurs get softer/better EXCEPT HOCM and MVP (get louder)
HOCM and MVP get louder
Atrial fibrillation on EKG
Absent P waves
Irregularly irregular R-R interval
MC arrhythmia in mitral stenosis d/t LA enlargement
Increases freq. of TIA/stroke
SVT on EKG
Sawtooth' complexes: Regular, narrow-complex tachy
No P waves and no fibrillatory waves
TX w/RF catheter ablation
Multifocal atrial tachy on EKG
Irregular P waves present = multiple foci of P waves
COPD (so no beta-blockers)
TX w/Ca2+ and digox
o True for all atrial arrhythmias
Ventricular tachy on EKG

Wide-complex tachy
Best initial therapy when hemodynamically stable is amiodarone
o Or lidocaine or procainamide
Also add MgO2 (esp. in torsade)
Defibrillate when hemodynamically unstable
o CP, SOB, hypotension/systolic less than 90, encephalopathic confusion
RBB on EKG
R-R' ('rabbit ears')
Greater than 120 ms
Tall R waves in V1, V2
LBB w/CP is an indication for thrombolytics and temp transvenous pacemaker
To confirm pleural effusion: Decubitus films to see if liquid is freely mobile
Widened mediastinum in person w/CP = aortic dissection
Difference in BP between arms
TEE has 95% accuracy in detection
Complement def'yrecurrent Neisseria infxns
HIV predisposes to PCP, but doesn't cause cardiac lesions