Signs and Symptoms

Many patients with Polycythemia vera may not know they have it. It is generally a slow and eventual process.  It may not be until they have routine blood work done, such as a CBC (Complete Blood Count), that their doctor is tipped off to something being wrong. The CBC of a patient with PV may show increased absolute Red Blood Cell count, increased Hemoglobin, as well as an increase in hematocrit percentage. Hemoglobin is major protein within a Red Blood cell that not only gives Red Blood cells their red hue, but it is also responsible for carrying oxygen throughout the body and to the tissues. It's no wonder that if the amount of Red Blood Cells increase, hemoglobin will generally follow and increase as well. The Hematocrit is a percentage of Red Blood Cells related to the total amount of blood volume. The remaining portion of blood volume that isn't Red Blood Cells, is mostly plasma. For some with PV, they can see a slight but generally not malignant increase in White Blood Cells as well as platelets. 

Normal RBC counts are roughly 4.5 to 6.0×10^12/L for men, and 4.0 to 5×10^12/L for women. Normal hemoglobin ranges 14 to 17 grams per deciliter(dL) for men and 12 to 15 grams per deciliter for women. Hematocrits range from 40-50% in men and 35-45% in women. Counts above this range, coupled with other symptoms could lead a doctor to suspect Polycythemia vera. Ranges will differ slightly based on location due to slight differences in instrumentation and patient population. 

Normal Blood Counts per MayoClinic laboratories

Polycythemia vera is dangerous however, because with an increase of Red Blood Cells beyond what is normal, the blood starts to become thicker and less viscous. This makes circulating the blood throughout the body much more difficult and can lead to dangerous situations such as blood clots and strokes. The situation in which the thickening, or an increase of viscosity of the blood, is called hyperviscosity syndrome. It is not specific to PV, and patient's with other hematologic malignancies such as Waldenstroms macroglobulinemia, leukemias, Multiple Myeloma, etc. Patient's with PV that start to experience hyperviscosity syndrome can expect to see most non-specific symptoms such as 
  • Headache
  • Nausea
  • Vision Changes and retinopathy
  • Dizziness/Vertigo
  • Seizures and potentially even coma. 
  • Dyspnea (Shortness of breath)
  • Fatigue/Weakness
  • Stroke
  • Night Sweats
  • Bruising / Extended Bleeding
  • Weight Loss

Nearly one fifth of all patients with PV are found to have clots within their circulatory system. A large majority of clots can cause and/or be related to stroke or TIAs (Transient Ischemic Attacks aka Mini-stroke).

Increased blood viscosity in PV is related to decreased blood flow (ischemia), especially to the brain which leads to an increased risk of thrombotic (clotting) events. Similarly, clots and hyperviscous blood can cause organ damage throughout the body, as well as heart attacks. 

Other symptoms include

Erythromelalgia with blotchy, discolored, red skin. This is due to the increase of red blood cells in the body and the slower circulation of the cells. The skin may be warm to the touch as well. A burning pain sensation can also occur as parts of the vasculature in the extremities can get periodically blocked due to the viscous blood. 

Itchy skin, especially after a warm bath/shower -- nearly half of all patients with PV will have itchy skin. It can be the first symptom to show before the disease progresses. It is thought that this is caused by an abnormal function of histamine release as well as cytokine release. (cytokines are cell signaling molecule)

Gout -- gout is a painful type of arthritis caused by an excess buildup of uric acid in the body. Uric acid crystals become deposited in areas of a patient's joints, usually causing immense pain. The big toe is the most common joint to experience this. In general gouty arthritis this is usually caused by the bodies failure to remove uric acid from circulation such as seen with a low functioning kidney. It can also be due to excessive intake through foods, etc. In the case of PV, it is related to the high turnover of Red Blood Cells causing excess UA to be produced,  and potentially the decreased excretion of Uric Acid due to organ damage related to PV. Increased Uric Acid and gout is also related to the myelofibrosis that can sometimes be seen in PV patients. 

Splenomegaly -- an enlarged spleen. One of the spleen's important functions is filtering out and removing old or damaged Red Blood Cells. In PV, since there are so many Red Blood Cells, there is an marked increase in the amount of old/damaged Red Blood Cells that the spleen has to process. This causes the spleen to enlarge as it becomes overworked and the cells build up. If it becomes too large, patient's can feel discomfort in that area.  

Myelofibrosis --- a severe scarring of the bone marrow that can occur as part of the PV disease progression. Myelofibrosis is not unique to PV and can happen under many other conditions. Over time, after consistently overproducing cells for extended periods of time, the bone marrow can become so overrun by scar tissue from the damaging effects of over proliferation, that it is no longer able to effectively make cells. This results in a broad DECREASE in cells across the board. One could expect to see decreased Red Blood Cell counts at this point (resulting in anemia), as well as a decrease in White Blood Cell counts and Platelets. Not all patients will progress to Myelofibrosis but nearly 10% may. Myelofibrosis also increases the risk of having gout symptoms as seen above.