Diseases of RBC Flashcards
(26 cards)
Pyruvate kinase hemolytic anemia
- Dogs and Cats
- Variable degrees of regenerative anemias.
- Progressive iron overload due to chronic hemolysis leads to hemosiderosis and liver fibrosis
- Dogs diagnosed young
- Cats can be older when first diagnosed
Phosphofructokinase hemolytic anemia
dogs ONLY
– some have no clinical signs but most have persistent hemolytic anemia exacerbated by a sporadic hemolytic crises secondary to exercise-induced hyperventilation alkalemia
Hemophagocytic anemia
- Predisposition
- Describe the mechanism
- CxS
- DDX and Dx
- Prognisis
- Predisposed in: Bernese Mountain Dog, Rottie, Golden, and Flat-Coated Retriever
- Erythrophagocytosis -> regen anemia
Erythrophagocytic histiocytes demonstrate infiltrative growth patterns in the spleen, liver, lung, and bone marrow. - Often have splenomegaly and hepatomegaly
- Clinical signs of weight loss, anorexia, and lethargy
- ~50% have thrombocytopenia <100k
- Splenic histiocytes typically show more atypia (atypical mononuclear cell and multinuclear giant cells)
- Can differentiate from other histiocytic proliferative disorders by immunophenotyping for the beta-2 integrins CD11/CD18.
- Grave prognosis, MST 4 weeks
Antimicrobial that can cause non-regenerative anemia?
Chloramphenicol
Binding of fibrinogen to what receptor is essential for aggregation and clot retraction?
Platelet integrins and nonintegrin glycoprotein receptors play a critical role in adhesion (platelet–subendothelial matrix interactions) and aggregation (platelet-platelet association). The alpha-IIb-beta-3 complex (GPIIb/IIIa Glanzmanns thromboasthenia, Great Pyrenese Otterdog) is the most abundant platelet integrin and functions as the activation-dependent receptor for fibrinogen, fibronectin, and VWF.
Causes of prolonged BMBT?
Inherited thrombocytopathies:
- Impaired platelet adhesion and aggregation in vWD, a hereditary deficiency of vWF reported in various D breeds and rarely in cats. vWD can result in a bleeding time more than 3x normal.
- Disorders of platelet membranes (Glanzmann’s thrombathenia in Otterhounds and Great Pyrenees)
- Disorders of platelet secretion in Spitz and Basset thrombopathy and platelet granule storage pool deficiency in American Cocker Sp and feline Chediak-Higashi syndrome.
vWF disease characteristics and RX
- Normal platelet counts, normal PT/PTT -> need to do BMBT to test for primary hemostasis
BMBT prolonged – test VWF:Ag prior to testing for intrinsic platelet function defects - A PFA-100 will also show prolongation in Type 1 when VWF <30%
- IF platelet count over >100k, and PCV >30% then a prolonged PFA-100 indicates vWF OR thrombopathia
- Type 1 and III quantitative (can measure VWG:Ag, DNA testing), Type II qualitative need to diagnosis via documentation of the absence of high molecular weight multimers of VWF through a functional assay or via SDS-agarose gel electrophoresis. An ELISA measures plasma VWF:collagen-binding activity (CBA) -> this can only be done with high molecular weight multimers. Therefore, dogs with Type II VWD will have decreased VWF:CBA relative to VWF:Ag, it will be >2. Normal dogs and dogs with Type 1 VWB, ratio is 1.
- Treat with – fresh whole blood, FFP 10-15 ml/kgh, and cryoprecipitate 1U/10kg (product of choice as it has conc VWF)
Breed predispositions for type 1,2,3 VWD?
Type 1: Dorbie, Bernie, Corgi, Dutch Partridge, German Pincher, Goldendoodle, Irish Setter, Kerry Blue Terrier, Manchester Terrier, Papillon Poodle, Westie
Type 2: German Shorthaired pointer, German Wirehaired Pointer
Type 3: Dutch Kooiker, Scottish Terrier, Sheltie
Glazmann thrombathenia
-Specific defect
-Breed affected
-Diagnosis
Specific defect: absence of deficiency of the fibrinogen receptor GPLLb- IIIa
Breed affected: Otterhounds, Great pyrenees
Diagnosis: DNA testing
Chediak-Higashi syndrome
-Specific defect
-Breed affected
-Diagnosis
Specific defect: Associated with leukocyte and melanocyte abnormalities. Platelet storage pool disorder associated with lack of discernable dense granules and deficiency of ATP, ADP, serotonin, Ca2+ and Mg2=.
Breed affected: Persian
Diagnosis: Presence of characteristic granules in leukocytes (smear) and melanocytes (skin biopsy).
Drugs that cause acquired thtombocytopenia?
hydroxyethyl starch, NSAIDs, and cephalosporins
Clopidegrel:
MOA
– an irreversible platelet P2Y12 ADP receptor antagonist (ADP cannot bind to its site). Clopidogrel’s active metabolite irreversibly alters the ADP receptor causing the platelet to be affected for its lifespan (5-7 days)! Aka platelet function returns to normal by 7 days, important for patients that need surgery!
SE: GI (v, d, anorexia; decreases with giving at mealtimes) and non-regenerative anemias in cats receiving longterm, and obvi bleeding
Aspirin: MOA
irreversible inhibitor of COX-1, reducing prostaglandin and thromboxane synthesis. Thromboxane is a vasoconstrictor, facilitates platelet aggregation, and is a potent hypertensive agent.
Chediak-Higashi Syndrome (again)
- primary immunodeficiency with recurrent neutropenia and neutrophil function defects, as well as platelet function defects
- Persians with the blue smoke coat color
- Neuts, eos, and other cells contain abnormally fused
granules - G-CSF can partially correct Neutrophil function defects
Pelger-Huet Anomaly
- defective terminal granulocyte maturation (neuts and eos).
- Australian Shepherds overrepresented
- Function of granulocytes are NORMAL
Leukocyte Adhesion Deficiency (LAD)
- Type 1LAD
- Canine LAD
- mutations in leukocyte adhesion proteins that prevent the normal adherence and migration of WBC through luminal endothelium
- Type 1 LAD of Irish Setters – defect in beta-2 subunit, aka CD18
- Canine LAD – CD18 transcription reduced and other neutrophils defects noted
- Markered peripheral neutrophilia with nuclear hypersegmentation, along with absence of neuts in the tissues
- Pups gets omphlitis (infection of umbilical stump), lymphadenopathy, low BW, and febrile infections. Antibiotics cannot prolong life and most die by 2-3 months of age. **Some dogs can live with this for years
Trapped Neutrophil Syndrome
- autosomal recessive neutropenia in Border Collies.
- Peripheral neutropenia with a degenerative left shift, marked monocytosis, and myeloid hyperplasia in the BM with increased mature neutrophils.
- Craniofacial development can be abnormal in severely affected dogs, small size, and they present with recurrent infections.
PK deficiency
(Congenital White Blood Cell Disorders)
dogs and cats - develop progressive myelofibrosis, with time failure and decreased production in all cell lines
X-linked Severe Combined Immunodeficiency (X-SCID)
- Congenital White Blood Cell Disorders.
- mutations in the gene encoding the IL-2 receptor gamma chain. Affects developing CD4 and CD8 thymocytes.
Cardigan Welsh Corgis and Basset Hounds
Pups have stunted growth, chronic infections, and as maternal Ab wanes they rarely
live past 4 months. Hypoplastic thymus, increased circulating B lymphs, no T lymphs
Females need 2 copies of X mutation, males only need one
Autosomal Recessive Severe Combined Immunodeficiency
-defective recombination events during T and B lymphocyte maturation. Point mutation in the catalytic subunit of DNA-dependent protein kinase
-Pups have severe lymphopenia, decreased serum globulins, and marked lymphoid hypoplasia in the spleen, thymus, and other lymphoid tissues. Opportunistic infections or MLV cause of death
-Jack Russel Terriers!
Cyclic Hematopoiesis in Gray Collies
-cyclic neutropenia from a defect in trafficking of lysosomal membrane proteins. Cycles neuts every 2 weeks.
-Neuts are deficient in elastase and myeloperoxidase – aka frequent infections, must succumb by 6 months of age
-G-CSF eliminated neutropenic episodes, but didn’t correct functional defects
-The gray coat color results from the defect in melanocytes
Insertional mutations in the AP3B1 gene
Common Variable Immunodeficiency
lymphocyte functions deficits, including hypogammaglobulinemia and absence of B cells in LN.
Miniature Dachshunds and Cavalier King Charles with Pneumocystis carinii
Lysosomal Storage Disorders
abnormal granules accumulate in the cytoplasm of neuts, monocytes, and lymphocytes
Mucopolysaccharidosis type VI and type VII in dogs and cats
Manifests in neurologic signs
GM2 gangliosidosis results in abnormal vacuolation in the cytoplasm of peripheral leukocytes
Pemphigus Foliaceus
-Autoantibodies disrupt desmosomal adhesion between keratinocytes, inducing subcorneal pustules
-Dog autoantibodies against desmocollin-1
Signalment – Akitas and Chow Chows are predisposed.
- Reported in other breeds like English Bulldog, Dobie, Collie, and Australian Sheepdog
- Clinical signs – subcorneal pustule that can progress to secondary erosions/crusts.
- Initial lesions usually on face (esp nasal planum, dorsal aspect of nose, periocular region, and concave pinnae.
- More than half will progress toward the generalized phenotype that involve the trunk and paw pads
Dx: Acantholytic keratinocytes with non-degenerated neuts or eos (acantholysis unfortunately not specific for PF, can be seen with pyoderma or pustular dermatophytosis)
Dx based on a combo of 1)skin lesion type and distribution 2)exclusion of an infection 3) supportive histopath findings
Other dx testing – IHC demonstrating antikeratinocyte Abs but this also detected in other dermatoses, serum antikeratinocyte Abs however this is also detected in low levels in healthy dogs, and finally anti- desmocollin-1 Abs but not commercially available
Tx: Steroids 2-4 mg/kg, and secondary immunosuppressives in some like cyclosporine
