other red cell disorders

Question 1

relative polycythemias

Answer 1

dehydration (water deprivation, vomiting, diarrhea, diuretics)
stress polycythemia/baisbock syndrome- HTN, obese, anxious, unknown etiology

Question 2

primary absolute polycythemias

Answer 2

intrinsic abnormality of hematopoietic precursors
PCV (MPD) most common
rare inherited erythropoietin receptor mutations

Question 3

secondary absolute polycythemias

Answer 3

red cell progenitors respondning to increased erythropoietin

Question 4

compensatory causes of secondary absolute polycythemias

Answer 4

lung disease
high altitude
cyanotic heart disease

Question 5

paraneoplastic causes of secondary absolute polycythemias

Answer 5

erythropoietin secreting tumors: renal cell carcinoma, hepatocellular carcinoma, cerebellar hemagioblastoma

Question 6

inherited defects causing secondary absolute polycythemias

Answer 6

VHL

prolyl hydroxylase mutations

Question 7

general causes of hemorrhagic diatheses

Answer 7

increased fragility of vessels
platelet deficiency or dysfunction
drrangement of coagulation

Question 8

PT

Answer 8

prothrombin time
extrinsic and common coagluation pathways
factor V, VII, X

Question 9

PTT

Answer 9

partial thromboplastin time
intrinsic and common pathwyas
V, VIII, IX, X, XI, XII, prothrombin, fibrinogen, or interfering Abs to phospholipis

Question 10

bleeding disorders caused by vessel wall abnormalities

Answer 10

relatively common, not usually serious bleeding
small hemorrhages in skin or mucous membranes
rarely into joints, mm, subperiosteal, GI, nosebleeds

Question 11

causes of bleeding disorders caused by vessel wall abnormalities

Answer 11

infections
drug rxns
connective tissue disease
hencoh-schonelein purpura
hereditary hemorrhagic telangiectasia- most serious
perivascular amyloidosis

Question 12

infections causing bleeding disorders caused by vessel wall abnormalities

Answer 12

petechial and purpuric hemorrhages of chest and back
mengiococcemia
septicemia
infective endocarditis
ricketssial diseases
vasculitis, DIC

Question 13

drug rxns bleeding disorders caused by vessel wall abnormalities

Answer 13

petchiae and purpura w/o thrombocytopenia

depostion of ICs in vessel walls -? leukcocytoclastic vasculitis

Question 14

CT disorders bleeding disorders caused by vessel wall abnormalities

Answer 14

scurvey
ehlers-danos syndrome
cushings
microvascular bleeding

Question 15

henoch-schonelein purpura

Answer 15

systemic immune disorder of unknown cause
purpuric rash, colicky abdominal pain, polyarthralgia, acute glomerulonephritis
deposition of IgA in glomeruli and elsewhere

Question 16

hereditary hemorrhagic telangiectasia

Answer 16

aka weber-osler-rendu syndrome
autosomal dominant
mutations in proteins which regulate TGFbeta signaling
dilated torturous blood vessels w/thin walls
bleeding most common from nose
this is most serious of vessel wall bleeding disorders

Question 17

thrombocytopenia

Answer 17

<20,000 spontaneous bleeding

normal PT and PTT

Question 18

causes of thrombocytopenia

Answer 18

decreased platelet production
decreased platelet survival
sequestration
dilution- massive transfusion

Question 19

decreased platelet survival

Answer 19

immune thrombocytopenia- destruction due to Abs on platelets (IgG from mom)
DIC, and thrombocytic microangiopathies
mechanical injuries

Question 20

chronic ITP

Answer 20

Ab mediated destruction of platelets

secondary due to SLE, HIV, B-cell neoplasms (CLL)

Question 21

chronic ITP pathogenesis

Answer 21

Abs most often directed against platelet membrane glycoproteins IIb-IIIa or Ib-IX
almost always IgG
usually marked improvement with splenectomy b/c less opsonization and less Ab production
Abs may also bind and damage megakaryocytes

Question 22

ITP morphology

Answer 22

principal changes found in spleen, bone marrow, and blood, but not specific
spleen normal size w/prominent reactive germinal centers
marrow reveals a modestly increased number of megakaryocytes
peripheral blood often reveals abnormally large platelets

Question 23

ITP clinical

Answer 23

chronic ITP occurs most commonly in adult women <40
characterized by bleeding into skin and mucosal surfaces
petechiae, especially where capillary pressure is high
may manifest first w/melena, hematuria, or excessive menstruation
brain hemorrhages serious and fatal
spleneomegaly and lymphadenopathy are uncommon
PT and PTT normal
Dx of elxusion
almost all respond to corticosteroids
splenectomy work in 2/3

Question 24

Acute ITP

Answer 24

mainly disease of childhood, equal M:F
Abs against platlets
1-2 wks post viral illness
self-limiting glucocorticoids only if severe
20%, persist to chronic form, these kids usually do not have viral prodrome

Question 25

drug induced thrombocytopenia

Answer 25

quiniine quinidine vancomycin all bind platelet glycoproteins and recognized as Ags also seen in platelet inhibitory drugs that bind glycoprotein IIb/IIIa HIT

Question 26

HIT

Answer 26

heparin induced thrombocytopenia | 5% of people who receive heparin

Question 27

HIT type I

Answer 27

rapid onset after heparin administration little clinical importance dont discontinue heparin

Question 28

HIT type II

Answer 28

less common 5-14 days after therapy begins life threatening thrombosis Abs recognize heparin and platlet factor 4 complexes

Question 29

HIV-associated thrombocyotpenia

Answer 29

one of most common hematological manifestations of HIV CD4 and CXCR4 (R and coR for HIV) found on megakaryocytes -> once infected prone to apoptosis HIV also causes B-cell hyperplasia increasing probability of autoAbs

Question 30

thrombotic microangiopathies

Answer 30

caused by insults that lead to excessive platelet activation intravascular thrombi cause microangiopathic hemolytic anemia widespread organ dysfunction thrombocytopenia due to consumption of platlets unlike DIC activation of coagulation cascade, not primary importance therefore PT and PTT normal

Question 31

TTP

Answer 31

thrombotic thrombocytopenic purpura pentad of fever, thrombocytopenia, micorangiopathic hemolytic anemia, transient neurological deficits, renal failure not all 5 must be present ADAMTS13 deficient (acquired more common then hereditary) plasmaphoresis

Question 32

ADAMTS13

Answer 32

vWF metalloprotese

Question 33

HUS

Answer 33

``` micorangiopathic hemolytic anemia thrombocytopenia acute renal failure may have fever and neuro issues children normal ADAMTS13 ```

Question 34

typical HUS

Answer 34

E. coli H7 -> shigga like toxin | children and older adults

Question 35

atypical HUS

Answer 35

``` defects in C' factor H cofactor protein CD46 factor I all of these usually prevent excessive activation of alternative C' pathway can be seen in pregnancy ```

Question 36

bleeding disorders related to platelet dysfunction categories

Answer 36

defects of adhesions defects of aggregations disorders in platelet secretion acquired

Question 37

bernard-soulier syndrome

Answer 37

defect in adhesions of platelets to subendothelial matrix inherited deficiency of Ib-IX variable, often severe bleeding

Question 38

glanzmann thrombasthenia

Answer 38

autosomal recessive deficiency of IIb-IIIa bleeding often severe

Question 39

disorders of platelet secretion

Answer 39

storage pool disorders

Question 40

acquired bleeding disorders related to platelet dysfunction

Answer 40

ingestion of aspirin and other NSAIDs | Uremia

Question 41

hemorrhagic diatheses related to abnormalities in clotting factors

Answer 41

often occurs into GI and urinary tract and weight bearing joints Vit K deficiency - II, VII, IX, X, protein C DIC- all factors used up

Question 42

VIII

Answer 42

essential cofactor for activation of X made in endothelium and kupffer cells in circulation binds vWF which increases its half life measured w/coagulation assays mixing patients plasma and factor VIII- deficient plasma

Question 43

vWF

Answer 43

produced by endothelium and megakarocytes stabilizes VIII measured w/ristocetin agglutination test where ristocetin cofactor would be decreased

Question 44

von Willebrand disease

Answer 44

most common inherited bleeding disorder of humans bleeding tendancy is usually mild, often goes unnoticed until trauma autosomal dominant 3 types

Question 45

vW disease types 1 and 3

Answer 45

``` quantitative defects autosomal domiinant make up 70% of cases type 1 mild bleeding type 3 severe deficiency -> makes VIII unstable -> severe bleeding prolonged PTT ```

Question 46

type 2

Answer 46

normal amount of vWF, dysfunctional 2a most common autosomal dominant mild-moderate bleeding

Question 47

hemophilia A

Answer 47

factor VIII disease most common hereditary disease associated w/life threatening bleeding x-linked recessive 30% acquired severe disease 1-5% VIII moderate disease >5% mild disease easy bruising, massive hemorrhage from trauma spontaneous bleeding into joints (hemarthroses) petechiae usually absent prolonged PTT and normal PT

Question 48

hemophilia B

Answer 48

``` christmas disease factor IX deficiency clinically indistinguishable from hemophilia A X-linked recesive PTT prolonged and normal PT ```

Question 49

DIC

Answer 49

acute, subacute, or chornic thrombohemorrhagic disorder characterized by excessive activation of coagulation and formation of thrombi in microvasculature not a primary disease

Question 50

normal clotting

Answer 50

initiated by exposure of tissue factor which combines w/factor VII to activate factor X and IX -> thrombin -> converts fibrinogen -> fibrin -> feeds back and activated IX, VIII and V, stimulates cross linking of fibirn -> stabilizes clot

Question 51

thrombin

Answer 51

swept away from site of injury and converted to anticoagluant by binding thrombomodulin -> activates protein C -> inhibits V and VIII

Question 52

2 mechanisms for DIC

Answer 52

release of TF or other procoagulant | widespread injury to endothelium

Question 53

release of TF or other procoagulants

Answer 53

placenta in obstetric complications (most commoni) trauma or burns mucous from certain adenocarcinomas

Question 54

morphology of DIC

Answer 54

bilateral renal cortical necorsis if severe fibrin degradation products alveolar thrombi-> pulmonary edema -> hyaline membranes -> ARDS

Question 55

endocrine syndromes and DIC

Answer 55

waterhouse-friderichsen syndrome | kasaback-merrti syndrome

Question 56

clinical DIC

Answer 56

acute DIC - bleeding | chronic DIC thrombotic

Question 57

febrile nonhemolytic reaction

Answer 57

most common complication of transfusion fevers, chills sometimes mild dyspnea

Question 58

allergic rxns to transfusion

Answer 58

IgA deficient patients- severe, rare IgG binds donor IgA | urticarial rxns- allergen in donor blood recongnized by IgE, generally mild, do not need to discontinue transfusion

Question 59

acute hemolytic reactions

Answer 59

usually typing or labeling error -> mismatched blood type fever, shaking, chills, flank pain positive direct coombs test can be fatal

Question 60

delayed hemolytic rnxs

Answer 60

``` IgG positive direct coombs low haptoglobin and elevated LDH Ags: Rh, Kell, Kidd can be as sever as blood type mismatch ```

Question 61

TRALI

Answer 61

transfusion related acute lung injury severe frequently fatal rxn that activates neutrophils in lungs rare, but more common in lung disease 2-hit hypothesis Abs often from multiparous women more likely with fresh frozen plasma and platelets pulonary edema that does not respond to diuretics

Question 62

infectious complications

Answer 62

most bacterial arise from skin flora | significant bacterial contamination ore common in platelets