Liver – synthesizes almost all clotting factors, stores vit K, filters damaged RBCs

Spleen – produces fetal RBC, filters, immune function, and stores platelets

Clotting Factors

 Vit K – stored in liver, found in dark, leafy greens and own intestinal bacteria (newborn’s
need a shot). Deficiencies can be caused by antibiotics, liver disease, gall bladder disease
(fat soluble vitamin which needs bile to be stored).
 Von Willebrand factor – needed for platelets to adhere (with factor VIII)
 Calcium (factor IV)- needed to initiate coagulation cascade to form a stable clot

Hemostasis  vasospasm platelet activation, hemostatic plug, coagulation, stable clot.

 Coagulation cascade can be intrinsic (PTT, 25-35 seconds) or extrinsic (PT, 10-15
seconds). Eventually they join and thrombin is produced to covert fibrinogen to fibrin
and form a stable clot.

Platelets/Thrombocytes – 150,000-400,000, thrombopoietin produced by liver, sleep, and

bone marrow stimulates production of platelets when they start to aggregate (are needed).
Have prostaglandins and release 2 granules for hemostasis.

 Clots need to dissolve so clot retraction (shrinking of clot) happens within 20-60
minutes, clot dissolution happens shortly after the clot is formed. Plasminogen (released
from platelets converts to plasmin which digests fibrin to dissolve clot.

Thrombocytosis – too many platelets, causes hypercoagulability. Can be caused by any

endothelial injury/inflammation (think inflammation and then clot).

Thrombocytopenia – too little platelets, below 20,000 can have spontaneous bleeding. Caused
by low production, increased breakdown (autoantibodies or excessive consumption), splenic
sequestration, transfusions (relative).

 Manifestations – ecchymosis, prolonged bleeding, petechiae, hematochezia, menaturia,

hematemesis, bleeding gums, purpura, epistaxis, intracranial bleeding – THINK
INCREASED BLEEDING
 Immune Thrombocytopenic Purpura (ITP)
o Cause: auto immune destruction of platelets in spleen by macrophages
o Manifestations – seen in children, chronic in adults. Classic symptoms of
thrombocytopenia and splenomegaly (spleen enlargement because it’s working
so hard)
 Drug-Induced Thrombocytopenia
o Cause – heparin induced (blood thinner) body produces antibodies, immune-
mediated response that aggregates platelets and then destroyed.
o Manifestations – possible thrombosis or clotting because of aggregation of
platelets and then thrombocytopenic because using all the platelets up
  Disseminated Intravascular Coagulation – not a disease, response to disease, clotting
and bleeding simultaneously. Massive clotting cascade which leads to a decrease
because increased consumption so can’t clot and then bleed out.
o Cause – sepsis, trauma, shock (any massive inflammatory response causes DIC)
o Manifestations – thrombotic symptoms (ischemia/tissue death, pulmonary
embolism, organ failure) AND bleeding symptoms (pallor, tachypnea,
tachycardia, neuro, oozing from venipuncture sites). First symptom post-surgery
is hemorrhage from surgical site.
 Von Willebrand Disease
o Cause – autosomal dominant deficiency of von Willebrand disease
o Manifestations – mild symptoms, bleeding from minor injuries
 Hemophilia A
o Cause – X linked (effects males more) recessive genetic disorder factor VIII
deficiency/gene mutation
o Manifestations – bruising, subdural hematomas/nerve compression,
hemarthrosis (bleeding in joint, can be bad)

Erythrocytes/RBCs- 4.5-5.5 – concave shape d/t fibrous proteins, transport O2 by hemoglobin,

lifespan is 120 days. Produced in response to decreased blood oxygen. Kidneys get angry and
secrete erythropoietin which stimulates bone marrow to produce reticulocytes (immature
RBCs, nucleated and mature into RBCs in 1-2 days). Hemoglobin (2 alpha, 2 beta chains which
each hold a heme unit and O2 binds to heme groups).

 Hemolysis of RBCs eventually they get weak and break and are destroyed by spleen and
then conjugated by liver to bilirubin and then is excreted. Iron is returned to bone
marrow and liver by transferrin, some excreted but most recycled. Stored in the liver as
ferritin.

Anemia – decrease in functional RBCs which results in hypoxia (increased HR, chest pain,
increased RR and depth, SOB/dyspnea, impaired healing, headache, jaundice). Can be gradual
or sudden and magnitude (lower more likely to have symptoms with lower hemoglobin level).

 Iron-deficiency anemia (microcytic, hypochromic) – most common, small and pale cells
o Risk factors – poverty, women, children that drink cow’s milk, M>F in
childhood/adolescents then F>M
o Etiology – inadequate intake, blood loss, malabsorption, and increased demand
(growth/pregnancy)
 Slow developing in 3 stages
 Stores depleted, deficient cells produced, and deficient cells
released
o Cell appearance – low hemoglobin, serum iron and ferritin, poikilocytosis
(irregularly shaped), anisocytosis (irregularly sized)
o Manifestations – koilonychia (spoon nails), glossitis, pica, cheilitis, cold
sensitivity, weakness and fatigue, classic anemia manifestations
 Megaloblastic anemia (macrocytic, normochromic) – large cells that have impaired
DNA synthesis, so they die within weeks opposed to months which decreases the
amount causing anemia
o Pernicious (B12/cobalamin) deficiency – lack of B12, need intrinsic factor
(produced by parietal cells in stomach) to absorb B12.
 Causes – autoimmune Type A chronic atrophic gastritis (destroys parietal
cells), long term use of H2 receptor blockers, nutritional deficiency
(vegan), malabsorption syndromes, and GI surgery
 Manifestations - **NEURO** issues which can be irreversible, general
symptoms of anemia, glossitis, hepato/splenomegaly, diarrhea, MVC
greater than 100, low HCT, low HGB.
o Folic acid deficiency – need folic acid to make RBC
 Causes – malabsorption, inadequate intake, cancer, drugs
 Manifestations – NO NEURO symptoms, cheilitis/stomatitis, dysphagia,
diarrhea, MVC greater than 100, low HCT, low HGB.
 Normocytic/normochromic
o Aplastic – characterized by pancytopenia (bone marrow not making all cells)
 Cause – congenital or acquired (ionizing radiation, chemicals, viral and
bacterial agents), rare can see with radiation chemo treatment
 Manifestations – gradually or suddenly, symptoms are suppression of
ALL blood cells (bleeding, increased chance of infection, general anemia
symptoms)
o Anemia of chronic disease – second most common after iron deficiency
 Cause – develops 1-2 months after sustained disease, infectious and
inflammatory processes activate T cells and cytokines which suppress
erythropoietin which stimulates bone marrow to produce RBCs (i.e.
chronic renal failure, cancer, chronic liver failure, IBD, AIDs).
 Hemolytic anemia – destruction of RBCs at a rate that exceed production, third major
cause
 Cause – intrinsic (sickle cell) or extrinsic (chemo/radiation/disease
(autoimmune, renal) – RBCs start normal and damaged by external
factors)
 Manifestations – HGB molecules can accumulate in renal tubules which
can cause necrosis, general anemic symptoms
 Sickle Cell disease (intrinsic) – autosomal recessive disorder that affects the gene
production of normal hemoglobin (HbS = abnormal, which causes the RBC to stiffen and
elongate in response to lower O2 levels, cells live 10-20 days), fatal and incurable.
Increases RBC adhesiveness (causes occlusion, ischemia, and infarction) and destruction.
o Sickling episodes – triggered by low O2 (infection, dehydration, acidosis,
hypothermia), and can eventually lead to shock. Lots of pain!!
o Sickling crisis – severe, acute exacerbation, vaso-occlusive crisis, not one vessel
but multiple vessels and multiple organs at the same time.
 o Manifestations – usually asymptomatic until crisis, pain and swelling of joints,
pallor, jaundice, SOB, all vital organ failure, hepatomegaly, spleen atrophies
(auto splenectomy – sluggish BF to spleen, causes an increased risk of infection),
acute chest syndrome (atypical pneumonia).

Polycythemia – excessive RBCs (platelets and WBCs also increased), HCT greater than 50%. Can
be relative d/t hemoconcentration (dehydration/fluid loss looks like too many RBCs) or
absolute d/t increased demand for O2 (primary – polycythemia vera or
secondary/compensatory – lung disease, live at high altitudes)

 Polycythemia vera – excessive RBC production from bone marrow, increased blood
viscosity, Hgb and Hct, harder to circulate.
o Manifestations – interferes with cardiac output, blood flow, HTN, hearing and
vision difficulties, thromboembolism (increased platelets that eventually get
destroyed leading to hemorrhage), lower iron levels, splenomegaly, and can
progress to acute myeloproliferative neoplasm (cancer).