Cytopenias (platelets and neutrophils)

thrombocytopenia

low platelet

-clotting, bleeding, petechiae, purpura, easy bruising

thrombocytopenia classification

mild: >70

moderate: 20-70

severe: <20

easy bruising: <50

life threatening: <15

Thrombocytopenia: increased destruction of platelets

-Immune thrombocytopenia

-Thrombotic Microangiopathy

-Heparin-induced thrombocytopenia

-Disseminated intravascular coagulation

Immune thrombocytopenia pathophysiology

-acquired autoimmune

-IgG bind to glycoproteins on platelets > spleen removes them from circulation

-no glycoprotein IIb/IIIa = no aggregation

-spleen marks them for destruction and removes

ITP in adults can also cause

- T-cell mediated platelets destruction

- impairment of production center of platelets

ITP epidemiology

Primary: idiopathic in most adults

Secondary: due to another disease

-lupus, lymphoma, meds, infections (HIV), vaccine

Immune thrombocytopenia etiology

Children: predominantly post infection, self limited, less chronic disorder, 2-5 IgM

Adults: idiopathic, secondary causes likely, chronic course, 20-30, >60, women IgG

Immune thrombocytopenia symptoms

- musculocutaneous bleedings: epistaxis

- asymptomatic - viral illness

- fatigue

- meds

Immune thrombocytopenia signs

- non-blanching petechial rash or purpura

- nose bleedings, buccal and gingival

Immune thrombocytopenia diagnosis

- only thrombocytopenia with everything else looking normal

Immune thrombocytopenia treatment

- <30000 or significant bleeding should be treated

First line: Prednisone with/o IVIG

Thrombotic Microangiopathy overview

- formation of small blood clots in tiny blood vessels > damage to organs and tissue

-the excessive platelets used to make little clots = decreased amount in circulation

Thrombotic Microangiopathy two main types

TTP: thrombotic thrombocytopenic purpura

HUS: hemolytic uremic syndrome

TTP pathophysiology

-autoantibodies against ADAMTS-13 > vWF are out of control > call platelets that stick together > microthrombi > decreased platelets willy is holding them all

TTP symptoms and signs

"FAT RN"

-fever

-anemia

-thrombocytopenia

-renal failure

-neurological symptoms

TTP diagnosis

-decreased ADAMTS-13 activity

-hemolytic anemia PBS: schistocytes

TTP treatment

-plasma exchange (TPE)

If relapse: plasma exchange reinstituted

-rituximab: if ineffective

HUS pathophysiology shiga-toxin

-shiga toxin- mediated HUS > toxin mediated endothelial damage from undercooked meat w E. coli > platelets go to site of damage > less platelets in circulation

HUS pathophysiology complement-mediated

-complement protein issues > genetic mutation leads dysregulation of complement

HUS symptoms and signs

"HUSS"

-hamburger

-urinary symptoms

-shitting

-school age

HUS diagnosis

complement-mediated: mutation of genes encoding complement proteins

Shiga: Positive E. coli, decreased antibodies to shiga toxin

-elevated creatine

HUS: complement- mediated treatment

-plasma exchange (TPE)

-infusion of the anti-complement C5 antibody eculizumab

HUS: Shiga-toxin treatment

-diarrhea associated HUS: supportive care

TIP treatment overview

Plasma exchange (TPE): TTP and complement-mediated

-remove pathogenic factors, replace factors, no more pathology

RBC transfusion: severe anemia

Hemodialysis: severe kidney injury

when can you give TIP patients platelets

- if there is a true life threatening bleeding

Heparin-induced thrombocytopenia (HIT) pathophysiology

-acquired disorder

-IgG antibodies to heparin-platelet factor 4 complex > activated platelets independent of physiological homeostasis > thrombocytopenia and thrombosis

HIP symptoms and signs

-asymptomatic

-thrombosis in 50% of patients 30 days post diagnosis

HIT diagnosis

-new onset thrombocytopenia 50% drop within 5-14 days of initial exposure to heparin

- low 4T score

- PF4 heparin antibody ELISA

-ultrasound

HIT treatment

-discontinue heparin

-DTI until platelets go up then warfarin

Disseminated Intravascular Coagulation (DIC) pathophysiology

- uncontrolled activation of coagulation > depletion of coagulation factors > thrombocytopenia bc platelets are activated instead

Disorders associated with DIC

-know its a very sick patient

-sepsis

-cancer

-trauma

-burns

-pregnancy

DIC symptoms and signs

-BLEEDING: catheter and IV

-thrombosis (trousseau syndrome)

DIC diagnosis

"DDIC"

- D-dimer increase

-Dripping blood

-Ill very

-Clotting got us here

-increased PT and PTT

- decrease fibrinogen levels

DIC treatment

-assess and treat underlying cause

-establish baseline

-transfuse blood products

-follow platelets 4-12hr

-consider heparin if persistent bleeding

Thrombocytopenia: decreased production

-bone marrow failure

-bone marrow infiltration

-chemo/rad

-nutritional deficiency

-cyclic thrombocytopenia

Bone marrow failure

-congenital or acquired

-replacement of normal bone marrow by leukemic cells, plasma cell myeloma, lymphoma or non hemolytic tumors, infection

-abnormalities in cell lines

bone marrow failure diagnosis

-bone marrow biopsy and aspirate

chemotherapy and radiation

- direct toxicity to megakaryocytes, hematopoietic progenitor cells or both

nutritional deficiencies

-deficiency in folate

-deficiency in B12

nutritional deficiencies diagnosis

-serum folate

-serum B12

-serum iron

Neutropenia epidemiology

-white blood cell critical to host defense

-release cytokines

-large reserve stored in marrow

neutropenia is defined as

<1800

severe: <500

neutrophil count can be lower in certain pops

consequence of neutropenia

increased risk of infections

neutropenia etiology

-bone marrow: congenital, hairy cell leukemia, myelodysplasia

-non-bone marrow: meds, immune mediated, sepsis

neutropenia symptoms and signs

-stomatitis (inflammation in mouth)

-infection

-cellulitis, pneumonia

-neutropenic fever of unknown origin

neutropenia diagnosis

-CBC w Diff: <1800

-PBS: see forms of neutrophils

-medication review

neutropenia treatment

-identify and discontinue causative drugs

-myeloid growth factors

-condition specific treatment

-febrile neutropenia (fever) : fluoroquinolone

-fungal coverage: fluconazole