• smooth muscle contraction with vessel spasm causing decreased blood loss and thrombus formation begins.
• damaged endothelial cells encourage platelet adhesion, activation, and aggreation. Also source of von Willebrand factor
• Normal adjecent endothelial cell limit clot formation (thrombin and t-PA)

under 50

increase the risk for major hemorrhage

bone marrow Dz

immune Dz

infection

    tissue trauma

    tissue trauma→tissue thromboplastin release→ VII→ X→ Ca→ V → prothrombin  activator

triggered by damaged blood cells or contact of cells with a foreign surface

decrease in the number of platelets

most common cause of abnormal bleeding

marrow damage (RT, chemo)

idiopathic

chemicals (benzene, insecticides)

complication of viral hepatitis

drugs ( thiazide diuretics, alcohol)

malignancy (marrow infiltration)

             Multiple myeloma

              acute leukemias

              lymphoma

               myeloproliferative disorders

peripheral smear

 bleeding time

PT (prothrombin time) –eval extrinsic system and common path.

PTT (partial thromboplastin time)

TT (thrombin clotting time)

used for standardized results

normal is = 1

 evaluates intrinsic system & common  pathway measures

 I, II, V, VIII, IX, X, XI & XII

Normal = 30-40

evaluates platelet function

normal= 3-7 min

Autoimmune IgG disorder

often preceded by a viral URI

epistaxis

oral/ gingival bleeding

menorrhagia

rare splenomegaly

• ↓ platelets
•  ↑ PT/INR, PTT
•  ↑ bleeding time
•   bone marrow biopsy
•   platelet associated antibodies

acute ITP may resolve spontaneously

corticosteroids (provide good results)

platelet transfusion

splenectomy

Longer than 6 months

more common in women 20-50

autoimmune Dz

      TTP(Thrombotic Thrombocytopenic Purpura)

      HUS(Hemolytic Uremic Syndrome)

      DIC(Disseminated Intravascular Coagulation)

Rare, often fatal

idiopathic

familial

 marrow transplant complication

drugs(quinine,ticlopidine,interferon, tacrolimus, cyclosporin)

Can occur with preeclampsia (peri or postpartum) or post-transplantation

Fever

multiple small vessel occlusions in Kidney

CNS

 nhemolytic anemia with schistocytosis

             thrombocytopenia

             ↑ LDH

             ↑ indirect bilirubin

             normal coag tests

             possible ↑ BUN/Cr

prednisone

anti-platelet agents

Primarly children under 10

infection of E. Coli 0157:H7

 bloody diarrhea

 acute renal failure

thrombocytopenia

anemia

hemodialysis

Older children

Adults

   loose strands of vWF or fibrin are deposited in multiple small vessels→ damage to passing platelets→ significant  thrombocytopenia & anemia.

   Platelets are also destroyed within multiple small thrombi

weakness/confusion/coma

abd pain/ N/ V/ D

arrhythmias

milder fever

vomiting/ abd pain/ bloody diarrhea

usually no plasma exchange

 half require dialysis

can be fatal

corticosteroids for adults

plasma exchange- rare

Activation of entire coagulation pathway

Presentation varies from “low grade” with minimal thrombocytopenia & bleeding to dramatic with severe thrombocytopenia &  bleeding

 septicemia

viral infections

chemotherapy

vasculitis

 pregnancy complication (amniotic embolism, abruptio placenta, eclampsia, dead fetus syn, septic abortion)

 acute hemolytic transfusion rxn (ABOincompatibility)                

snake & viper venom

burns

liver disease (fulminant hepatic failure)

fibrinogen <100

increased fibrin split products

↑ bleeding time

↑ D-dimer 

thrombocytopenia

factor & platelet replacement

easy bruising

menorrhagia

 gingival bleeding

GI bleeding

↑ bleeding time

 norm/low factor VIII:C

↓ vWF antigen

avoid ASA, NSAIDs

replace vWF

DDAVP

 platelet transfusion

X-linked chromosome disorder, in males

Factor VIII

defect in intrinsic pathway

associated with spontaneous or excessive hemorrage

X-linked recessive disorder in males

factor IX deficiency

Sx are usally mild

seen in Ashkenazi Jews

 repeated, spontaneous bleeding

hemarthroses

 epistaxis

intracranial bleeding

 hematemesis

 melena

microscopic hematuria

bleeding into soft tissues & gingiva

norm PT, bleeding time, platelets

↓ factor VIII levels

 IV heat treated factor VIII conc

desmopressin

avoid ASA

 poor diet

 liver failure

 malabsorption

not eating well

on broad spectrum antibiotics

soft tissue bleeding

↑ liver enzymes

↓ levels vit K, factor II, VII, IX & X

parenteral vit K

FFP for hemorrhage

 inherited defects in coag factors

defects in the fibrinolytic sysytem

 inherited defects in coag factors and defects in the fibrinolytic sysytem, leading to a thrombic tendency, may play a role in patients who develop what?

DVT

PE

      DVT/PE < age 50 w/o a predisposing factor

      recurrent thrombotic events

      strong FHx of thromboembolic events

      thromboembolism during pregnancy or while taking estrogen

      factor V Leiden 

      20210 AG prothrombin gene mutation

      hyperhomocysteinemia

      AT-III deficiencies

      proteins  C & S deficiencies

      antiphospholipid antibodies

mutation on chromosome 1 has been detected in 20-60% of adults with a strong FHx of thromboembolic disease

         higher in those of Greek & Northern European descent

Intrinsic pathway

Monitor PTT every 6hrs for 48hrs

12-24hrs for therapeutic levels

reversed by protamine sulfate

         venous/arterial thrombosis

         PE

         systemic embolism with prosthetic heart valves

         A-fib

Extrinsic pathway

Monitored by PT/ INR Qday

3-4 days for full effect

can be started with heparin

Autosomal recessive trait in caucasians that casuses a excessve iron loading of tissues

              complication of liver disease or certain anemias

asthenia (unexplained chronic fatigue)*

loss of libido, impotence*

darkening of the skin*

insulin-dependent diabetes

arthralgias – small/large joints*

gonadal failure

cardiac failure/arrhythmias

cirrohsis

 abdominal pain (RUQ)

serum ferritin level >1000 µg/L

Transferrin sat >50%

bone marrow aspirate

liver bx

**genetic testing for HFE1 gene**

 aggressive iron unloading

                 phlebotomy

                 chelation – deferoxamine (DFO)

avoid all po iron preps

dietary restrictions are not necessary

 cirrohsis

cardiac complications- restrictive cardiomyopathy

pancreatic damage

liver neoplasm

     Thalassemia

     Sideroblastic anemias

     Dysplastic/megaloblastic anemias

     G6PD deficiency

    Transfusion hemosiderosis

     Porphyria cutanea tarda

     Alcoholic cirrohsis

 Classic (HFE) hemochromatosis (Type I)

Juvenile hemochromatosis (Type II)

 nElevated lead levels reduce the circulating red cell mass by inhibiting 3 enzymes in the heme synthesis pathway

nLead appears to injure the RBC membrane, possibly by inhibiting ATPase → impaired cation exchange

PBG synthase

       heme synthase

       coproporphyrinogen oxidase

     RBC stippling

      ringed sideroblasts on peripheral smear  

 urine, blood lead levels

speech & language deficits

learning problems

GI distress (constipation, vomiting)*

severe, diffuse abd pain with episodes of paralytic ileus (acute intoxication)*

 linear blue-black line in gingiva*

motor neuropathies

CNS damage

fatigue (anemia)

ALA synthase

&

Heme

PCT (porphyria cutanea tarda)

EPP (erythropoietic porphyria)

vesiculo/bullous eruptions

plaquelike scar formation

hyperpigmentation

excess hair to face

 begins inchildhood

itching,

burning,

erythema

angioneurotic,

edemalike swelling of  exposed skin areas

cutaneous photosensitivity reactions

Lead poisoning

       EPP: mild hemolysis, hypochromia

       Lead poisoning:  prominent stippling of RBCs

nAggressive phlebotomy with cirrhosis & iron loading

before age 50

intravascular hemolytic anemia

hepatic dysfunction -  in children.Begins as hepatomegaly, fatty liver &  LFTs

neuropsychiatric illness – seen as a movement disorder or rigid dystonia or as psychiatric sx

hepatomegaly

elevated LFTs

fatty liver on u/s

Kayser-Fleischer rings on slit lamp (brown rings at corneal margins)

↓ serum ceruloplasmin

24-hr urinary copper excretion

-dietary elimination of copper rich foods (organ meats, shellfish, nuts, chocolate& mushrooms)

-filter home water with copper content

-chelation therapy with penicillamine (will provide varying degrees of improvement)

     CV failure→ death

Electrolyte Solutions

Ringer Lactate

Normal Saline

expand by 1 liter

3-4 liters need to be transfused rapidly

purified plasma protein fraction

hydroxyethyl starch solution

200ml of plasma

                   coag factors: fibrinogen

                                         prothrombin

                                         factors XI, IX, VIII, X, V & VII

FFP is a protein expander

induce IgE mediated allergic rxn

whole blood

platelets

coagulation factors

       PRBCs

      Leukodepleted RBCs

      Washed RBCs

      Frozen(deglycerolized RBCs)

      Irradiated red cells

      CMV-negative red cells

       Pooled random donor

       Single donor pharesis

       HLA-matched single donor

       FFP

       Cryoprecipitate

Used to treat most anemias

contains=RBC, WBC, and platelets

       reduces HLA allo-immunization, CMV

        transmission

RBC's are repeatedly washed & suspended in saline. Removes

most WBCs & 99% of plasma

      for long term storage of those with rare blood types

Improve O2 delivery to tissues

not to treat hypovolumia

Hgb-1g/dl

Hct-3%

         Cryoprecipitate

emergency reversal of warfarin Rx

DIC

liver disease

inherited coagulopathies

 fibrinogen replacement

            chest & low back pain

            hypotension

            feeling of impending doom

Transfusion rxn occurs with the 2nd & subsequent

transfusions→hemolysis of donor RBCs

        Hemolytic disease of the newborn

Erythroblastosis fetalis

   brain damage or death can result

  1-2 exchange transfusions post birth